Phosphorylation of Histone H2AX and Activation of Mre11, Rad50, and Nbs1 in Response to Replication-dependent DNA Double-strand Breaks Induced by Mammalian DNA Topoisomerase I Cleavage Complexes

Name: Work Video:
Duration: 3 min 30 s
Takahisa Furuta; Haruyuki Takemura; Zhi-Yong Liao; Gregory J. Aune; Christophe E. Redon; Olga A. Sedelnikova; Duane R. Pilch; Emmy P. Rogakou; Arkady Celeste; Hua Tang Chen; André Nussenzweig; Mirit I. Aladjem; William M. Bonner; ﻿Yves Pommier
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2225, 2235, 2284, 2327, 2367, 2445, 2456, 2466, 2474, 2491, 2516, 2533, 2553, 2789, 2847], 'diverse': [5, 216], 'causes': [6, 217], 'in': [7, 72, 102, 113, 122, 138, 218, 283, 313, 324, 333, 349, 645, 722, 859, 1218, 1233, 1252, 1266, 1379, 1549, 1930, 2047, 2126, 2136, 2168, 2249, 2255, 2298, 2342, 2379, 2427, 2432, 2538, 2557, 2608, 2611, 2619, 2622, 2688, 2831, 2834, 2863, 2878, 2896, 2971, 3004, 3047, 3133, 3211, 3238, 3355, 3368, 3391, 3484, 3497, 3520, 3559, 3579, 3584, 3636, 3698, 3739, 3748, 3798, 3821, 3833, 3858, 3865, 3882, 3933, 3971, 3981, 4020, 4031, 4034, 4052, 4129, 4185, 4204, 4209, 4226, 4244, 4255, 4307, 4312, 4361, 4368], 'eukaryotic': [8, 219, 588], 'cells': [9, 48, 109, 117, 152, 220, 259, 320, 328, 363, 860, 1224, 1246, 1946, 2180, 2279, 2324, 2364, 2748, 3228, 3245, 3318, 3336, 3437, 3499, 3524, 3583, 3623, 3640, 3677, 3700, 3733, 3752, 3775, 3814, 3822, 3830, 3837, 3867, 4019, 4033, 4064, 4131, 4187, 4206, 4211, 4309, 4313], 'are': [10, 133, 153, 176, 197, 221, 344, 364, 387, 408, 474, 503, 1247, 1662, 1671, 1680, 1947, 1956, 3693, 4344], 'accompanied': [11, 222], 'by': [12, 191, 223, 402, 1241, 1334, 1361, 1371, 1545, 1592, 1620, 1689, 1870, 2001, 2006, 2402, 2763, 2773, 2814, 2850, 2985, 3030, 3093, 3200, 3379, 3384, 3406, 3425, 3557, 3606, 3853, 3965, 4003, 4169, 4202, 4263, 4291, 4337, 4353], 'the': [13, 51, 56, 64, 85, 93, 134, 142, 207, 224, 262, 267, 275, 296, 304, 345, 353, 418, 448, 454, 475, 548, 556, 567, 647, 651, 717, 1053, 1229, 1234, 1329, 1372, 1495, 1559, 1596, 1599, 1603, 1615, 1624, 1631, 1636, 1667, 1690, 1697, 1720, 1758, 1872, 1921, 1926, 1933, 1950, 1959, 1995, 2007, 2026, 2029, 2035, 2038, 2119, 2132, 2137, 2142, 2148, 2161, 2184, 2250, 2403, 2548, 2603, 2753, 2758, 2764, 2848, 2909, 2988, 2999, 3022, 3189, 3203, 3251, 3274, 3280, 3323, 3328, 3332, 3344, 3349, 3361, 3373, 3380, 3385, 3392, 3396, 3407, 3416, 3467, 3490, 3570, 3601, 3609, 3621, 3639, 3676, 3721, 3740, 3789, 3801, 3826, 3883, 3921, 3934, 3937, 3955, 3977, 4005, 4023, 4032, 4035, 4041, 4055, 4107, 4121, 4164, 4240, 4259, 4347, 4362, 4376], 'formation': [14, 25, 59, 80, 99, 140, 225, 236, 270, 291, 310, 351, 1042, 1996, 2008, 2120, 2146, 3451, 3511, 3614, 3632, 3728, 3795, 3852, 3863, 3996, 4122, 4165, 4201, 4225, 4306, 4352, 4359], 'of': [15, 144, 226, 355, 450, 545, 552, 555, 719, 747, 760, 795, 1055, 1231, 1236, 1324, 1331, 1364, 1374, 1498, 1561, 1595, 1598, 1630, 1699, 1722, 1760, 1923, 1935, 1961, 1997, 2009, 2028, 2037, 2121, 2139, 2164, 2252, 2335, 2409, 2480, 2551, 2589, 2747, 2786, 2854, 2892, 2998, 3128, 3219, 3254, 3265, 3287, 3297, 3317, 3322, 3331, 3335, 3341, 3348, 3423, 3469, 3495, 3600, 3604, 3620, 3638, 3675, 3723, 3742, 3791, 3800, 3828, 3842, 3887, 3957, 4040, 4054, 4109, 4116, 4123, 4166, 4199, 4242, 4364, 4378, 4385], 'phosphorylated': [16, 227, 745, 758], 'H2AX': [17, 228, 593, 639, 652, 704, 748, 1219, 1244, 2140, 2169], '(γH2AX)': [18, 229], 'foci.': [19, 230, 2128, 4297], 'Here': [20, 231], 'we': [21, 232, 2108, 3681], 'show': [22, 233], 'that': [23, 127, 234, 338, 582, 1493, 1751, 3431, 3509, 3573, 3611, 4062, 4119, 4158, 4220, 4289, 4332, 4349], 'γH2AX': [24, 58, 79, 98, 139, 185, 195, 235, 269, 290, 309, 350, 396, 406, 752, 855, 1034, 1040, 1079, 1232, 2122, 2145, 2165, 2567, 3424, 3445, 3449, 3496, 3510, 3519, 3554, 3578, 3590, 3605, 3612, 3630, 3679, 3687, 3726, 3744, 3793, 3851, 3861, 3963, 3994, 4009, 4025, 4028, 4048, 4069, 4072, 4167, 4180, 4200, 4223, 4243, 4296, 4304, 4335, 4351, 4358], 'is': [26, 100, 119, 237, 311, 330, 547, 569, 650, 856, 1043, 1328, 1489, 1575, 1590, 1613, 1618, 1753, 1801, 1937, 2032, 4355], 'also': [27, 238, 867, 2130, 3507, 3809, 4060, 4330], 'a': [28, 183, 239, 394, 426, 1047, 1056, 1362, 1490, 1546, 1551, 1562, 1568, 1580, 1746, 2017, 2022, 2048, 2281, 2554, 2558, 2666, 2720, 2731, 2741, 2924, 3260, 3306, 3502, 3618, 4082, 4113, 4227, 4380], 'cellular': [29, 240, 1804, 3370, 4006], 'response': [30, 186, 241, 397, 1267], 'to': [31, 37, 50, 74, 156, 165, 168, 178, 206, 242, 248, 261, 285, 367, 376, 379, 389, 417, 446, 453, 505, 1045, 1249, 1259, 1268, 1534, 1558, 1566, 1578, 1755, 1940, 2111, 2436, 2547, 2771, 2801, 2889, 2923, 2957, 3014, 3021, 3149, 3170, 3224, 3273, 3291, 3343, 3517, 3594, 3617, 3695, 3731, 3763, 3920, 3948, 4066, 4246, 4315], 'topoisomerase': [32, 52, 243, 263, 766, 1376], 'I': [33, 53, 244, 264, 1377, 2560], 'cleavage': [34, 245, 1573, 1581, 1660, 1868, 2024], 'complexes': [35, 205, 246, 416, 1661, 1869], 'known': [36, 247, 3694], 'induce': [38, 249, 2118, 3518, 3577, 4295], 'during': [42, 253, 432, 868, 1500, 3936], 'replication.': [43, 254], 'In': [44, 255, 637, 2105, 3720, 3788, 3803], 'HCT116': [45, 256, 2179, 3436, 3859, 3866, 3972], 'human': [46, 257, 3433, 3580], 'carcinoma': [47, 258, 2176, 3435], 'exposed': [49, 164, 260, 375, 2546, 4314], 'inhibitor': [54, 69, 88, 265, 280, 299, 4115, 4384], 'camptothecin,': [55, 266, 3792, 4018], 'resulting': [57, 268, 2046], 'can': [60, 81, 271, 292, 424, 1358, 1525, 2003], 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202, 301, 317, 321, 340, 361, 383, 386, 413, 436, 470, 519, 563, 592, 778, 870, 873, 1049, 1085, 1091, 1225, 1257, 1263, 1366, 1370, 1391, 1394, 1504, 1628, 1669, 1674, 1678, 1714, 1863, 1929, 2123, 2141, 2147, 2153, 2158, 2178, 2198, 2270, 2275, 2289, 2311, 2318, 2322, 2339, 2359, 2376, 2396, 2398, 2414, 2429, 2461, 2486, 2565, 2638, 2686, 2699, 2717, 2757, 2784, 2812, 2838, 2867, 2881, 2906, 2973, 2983, 3032, 3037, 3112, 3144, 3198, 3221, 3226, 3241, 3284, 3462, 3464, 3477, 3492, 3503, 3562, 3581, 3586, 3626, 3647, 3688, 3750, 3774, 3784, 3835, 3847, 3893, 3899, 3906, 3960, 3997, 4008, 4037, 4215, 4237, 4248, 4323, 4382], 'enhanced': [91, 302, 4303, 4334], 'checkpoint': [94, 203, 305, 414, 526, 1086, 2154, 4261, 4366], 'abrogator': [95, 306], '7-hydroxystaurosporine.': [96, 307, 828], 'This': [97, 308, 744, 1572], 'suppressed': [101, 312, 4163], 'ATR': [103, 128, 314, 339, 781], '(ataxia': [104, 315], 'telangiectasia': [105, 124, 316, 335, 777, 817, 2202, 2358], 'Rad3-related)': [107, 318], 'deficient': [108, 319], 'markedly': [111, 322, 4302], 'decreased': [112, 323], 'DNA-dependent': [114, 130, 325, 341, 803], 'protein': [115, 131, 204, 326, 342, 415, 804, 2884, 2893, 3110, 3130], 'kinase-deficient': [116, 327], 'but': [118, 329, 866, 4207, 4310], 'not': [120, 331, 4208, 4294, 4311], 'abrogated': [121, 332], 'ataxia': [123, 334, 769, 776, 816, 2201], 'cells,': [125, 336, 1932, 3725, 3806], 'indicating': [126, 337], 'kinases': [135, 346, 2134, 4389], 'primarily': [136, 347], 'involved': [137, 348], 'at': [141, 352, 716, 2034, 2246, 2315, 2424, 2600, 2625, 2657, 2680, 2816, 2819, 2840, 2870, 3095, 3102, 3120, 3155, 3234, 3319, 3400], 'sites': [143, 354, 718], 'replication-mediated': [145, 356, 2010, 2114, 4125], 'breaks.': [148, 359], 'Mre11-': [149, 360], 'Nbs1-deficient': [151, 362], 'still': [154, 365], 'able': [155, 366], 'form': [157, 169, 368, 380, 746, 759, 1260, 2418, 4067], 'γH2AX.': [158, 369, 3818], 'However,': [159, 370, 4298], 'H2AX-/-': [160, 371, 3222, 3227], 'mouse': [161, 372, 822, 1221, 2171, 2277, 2440, 3522, 3582], 'embryonic': [162, 373, 823, 1222], 'fibroblasts': [163, 374], 'camptothecin': [166, 377, 1936, 2110, 2590, 3255, 3342, 3441, 3454, 3515, 3607, 3764, 3854, 3940, 3966, 4170, 4221, 4264, 4338, 4354], 'fail': [167, 378, 1258], 'Mre11,': [170, 381, 2156], 'Rad50,': [171, 382, 1089, 2157], 'Nbs1': [173, 384, 1264], 'foci': [174, 196, 385, 407, 1080, 1265, 3446, 3745, 4073, 4168, 4181], 'hypersensitive': [177, 388, 1248], 'camptothecin.': [179, 390], 'These': [180, 391, 1243, 4217, 4342], 'results': [181, 392, 3567, 4218, 4343], 'demonstrate': [182, 393], 'conserved': [184, 395, 585], 'for': [187, 199, 398, 410, 429, 479, 509, 524, 1052, 1696, 1719, 1757, 1806, 1994, 2238, 2615, 2628, 2647, 2660, 2683, 2797, 2823, 2883, 2953, 2964, 3010, 3044, 3099, 3109, 3116, 3152, 3166, 3177, 3184, 3216, 3256, 3442, 3569, 3685, 3817, 3873, 3916, 3954, 4046], 'induced': [190, 401, 1240, 4262], 'fork': [193, 404, 2019, 2044], 'collision.': [194, 405], 'required': [198, 409, 3512], 'recruiting': [200, 411, 525], 'repair': [201, 412, 451, 477, 1084, 1235, 1505, 2152], 'break': [209, 420, 1059, 1255, 2051, 2151], 'sites.': [210, 421], 'Compact': [422], 'chromatin': [423, 442, 507, 546], 'structural': [427], 'barrier': [428], 'processing': [431], 'replication,': [433, 1501], 'transcription,': [434, 1502], 'recombination,': [435, 1503], 'repair.': [438], 'Following': [439], 'damage,': [441], 'must': [443], 'modified': [445, 2257, 2381], 'permit': [447], 'access': [449], 'proteins': [452, 527, 1087, 2920], 'lesions': [456, 1369, 2000, 3576], '(1Smerdon': [457], 'M.J.': [458, 940, 944, 975, 1184, 1289], 'Biochemistry.': [459, 628], '1983;': [460], '22:': [461, 617, 1707], '3516-3525Crossref': [462], 'PubMed': [463, 496, 537, 604, 619, 632, 673, 699, 739, 850, 896, 915, 930, 961, 1002, 1028, 1074, 1115, 1160, 1211, 1316, 1350, 1409, 1434, 1462, 1516, 1654, 1709, 1731, 1794, 1841, 1857, 1899, 1915, 2070, 2083, 3547, 3666, 3715, 4099, 4150], 'Scopus': [464, 497, 538, 605, 620, 633, 674, 700, 740, 851, 897, 916, 931, 962, 1003, 1029, 1075, 1116, 1161, 1212, 1317, 1351, 1435, 1463, 1517, 1655, 1710, 1795, 1842, 1858, 1900, 1916, 2071, 2084, 3548, 3667, 3716, 4100, 4151], '(25)': [465], 'Google': [466, 499, 540, 607, 622, 635, 676, 702, 742, 853, 899, 918, 933, 964, 1005, 1031, 1077, 1118, 1163, 1214, 1319, 1353, 1410, 1437, 1465, 1486, 1519, 1657, 1712, 1732, 1743, 1797, 1819, 1844, 1860, 1902, 1918, 1976, 1989, 2073, 2086, 2103, 3550, 3669, 3718, 4102, 4153, 4282, 4408], 'Scholar).': [467, 500, 541, 636, 703, 743, 854, 1032, 1078, 1119, 1320, 1354, 1487, 1520, 1658, 1744, 1798, 1861, 1919, 1990, 2104, 3551, 3670, 3719, 4103, 4154, 4283], 'Homologous': [468], 'recombination': [469, 872], 'non-homologous': [471], 'end': [472, 511, 1627], 'joining': [473], 'main': [476], 'pathways': [478], '(2van': [483], 'Gent': [484], 'D.C.': [485], 'Hoeijmakers': [486], 'J.H.': [487], 'Kanaar': [488, 1062], 'R.': [489, 969, 1063, 1147, 1810, 2059, 2095, 2287, 4139], 'Nat.': [490, 1508], 'Rev.': [491, 1509], 'Genet.': [492, 668], '2001;': [493, 999, 1066, 1347, 1406, 1483], '2:': [494], '196-206Crossref': [495], '(965)': [498], 'Both': [501], 'processes': [502], 'assumed': [504], 'require': [506], 'alterations': [508], 'processing,': [512], 'strand': [513, 1544, 1606, 2031], 'invasion,': [514], 'branch': [515], 'migration,': [516], 'synthesis,': [518], 'ligation': [520], 'as': [521, 523, 1528, 1579, 2740, 2766, 3327, 3360, 3649, 3979], 'well': [522, 3240, 3299], '(3Green': [528], 'C.M.': [529], 'Almouzni': [530], 'G.': [531, 1415, 1442, 2093, 3534], 'EMBO': [532], 'Rep.': [533], '2002;': [534, 670, 1157, 1208, 1313, 1454, 1513, 1791, 1816], '3:': [535, 1514], '28-33Crossref': [536], '(179)': [539], 'The': [542, 1521, 1531, 1991, 2189, 2220, 2501, 2522, 2704, 2736, 2781, 2826, 2859, 2874, 2918, 2932, 2967, 3105, 3158, 3206, 3244, 3294, 3315, 3365, 3991, 4231], 'fundamental': [543], 'unit': [544], 'nucleosome,': [549], 'which': [550, 566, 1550, 3673], 'consists': [551], 'an': [553, 1802, 2200, 4252], 'octamer': [554], 'four': [557, 3779], 'core': [558], 'histones,': [559], 'H2A,': [560, 643], 'H2B,': [561], 'H3,': [562], 'H4,': [564], 'around': [565, 1602], 'bound.': [570], 'Histone': [571], 'H2A': [572, 649], 'includes': [573], 'three': [574, 3187], 'subfamilies': [575], 'whose': [576], 'members': [577], 'contain': [578], 'characteristic': [579], 'sequence': [580], 'elements': [581], 'have': [583, 1227], 'been': [584, 714, 750, 1687, 1717], 'independently': [586], 'throughout': [587, 1666, 1925], 'evolution:': [589], 'H2A1-H2A2,': [590], 'H2AZ,': [591], '(4Pehrson': [594], 'J.R.': [595], 'Fuji': [596], 'R.N.': [597], 'Nucleic': [598, 613], 'Acids': [599, 614], 'Res.': [600, 615, 1405, 1482, 1815, 1972, 1985, 2099, 4278, 4404], '1998;': [601, 691, 842, 888, 1651, 4405], '26:': [602], '2837-2842Crossref': [603], '(122)': [606], 'Scholar,': [608, 623, 677, 900, 919, 934, 965, 1006, 1164, 1411, 1438, 1466, 1733, 1820, 1845, 1903, 1977, 2074, 2087], '5Thatcher': [609], 'T.H.': [610], 'Gorovsky': [611], 'M.A.': [612], '1994;': [616, 1854, 1912], '174-179Crossref': [618], '(174)': [621], '6West': [624], 'M.H.': [625], 'Bonner': [626, 664, 686, 731, 837, 883, 907, 951, 990, 1015, 1103, 1201, 1306, 3658, 4091], 'W.M.': [627, 687, 732, 838, 884, 908, 952, 991, 1016, 1104, 1202, 1307, 3659, 4092], '1980;': [629], '19:': [630], '3238-3245Crossref': [631], '(219)': [634], 'mammals,': [638], 'represents': [640], '2–25%': [641], 'total': [642, 3129], 'whereas': [644, 3738, 4027, 4071], 'yeast,': [646], 'major': [648], 'ortholog': [653], '(7Redon': [654], 'C.': [655, 728, 730, 904, 906, 987, 1012, 1139, 1186, 1291, 1964, 3532, 3655, 3657, 4088, 4090], 'Pilch': [656, 680, 831, 877, 984, 1187, 1292], 'D.': [657, 1968, 2053, 4133], 'Rogakou': [658, 947, 1095], 'E.': [659, 1182, 1287], 'Sedelnikova': [660, 1175, 1280], 'O.': [661, 1172, 1277], 'Newrock': [662], 'K.': [663, 1141, 1200, 1305, 1764, 1778, 1780, 2291], 'W.': [665, 1010], 'Curr.': [666, 1064, 1105], 'Opin.': [667], 'Dev.': [669], '12:': [671], '162-169Crossref': [672], '(633)': [675], '8Rogakou': [678], 'E.P.': [679, 726, 830, 876, 902, 948, 1008, 1096, 3653, 4086], 'D.R.': [681, 832, 878, 985, 1188, 1293], 'Orr': [682, 833, 879], 'A.H.': [683, 834, 880], 'Ivanova': [684, 835, 881], 'V.S.': [685, 836, 882], 'J.': [688, 733, 839, 885, 909, 942, 1017, 1127, 1451, 1789, 3660, 4093], 'Biol.': [689, 735, 840, 886, 911, 1018, 1065, 1106, 1452, 1512, 2066, 2079, 3662, 4095, 4146], 'Chem.': [690, 841, 887, 1019, 1453], '273:': [692, 843, 889], '5858-5868Abstract': [693, 844, 890], 'Full': [694, 696, 845, 847, 891, 893, 1023, 1025, 1069, 1071, 1110, 1112, 1457, 1459], 'Text': [695, 697, 846, 848, 892, 894, 1024, 1026, 1070, 1072, 1111, 1113, 1458, 1460], 'PDF': [698, 849, 895, 1027, 1073, 1114, 1461], '(4203)': [701, 852, 898], 'phosphorylation': [705, 2138], '(at': [706], 'its': [707, 1675, 1864, 2124], 'C': [708], 'terminus': [709], 'on': [710, 2542, 2581, 3042, 3850, 3962], 'serine': [711], '139)': [712], 'has': [713, 749, 1685, 1716], 'found': [715, 4061], 'chromosomal': [723], '(9Rogakou': [725, 3652, 4085], 'Boon': [727, 903, 1011, 3654, 4087], 'Redon': [729, 905, 986, 1185, 1290, 3656, 4089], 'Cell': [734, 910, 2173, 3089, 3123, 3661, 4094, 4232], '1999;': [736, 912, 1706, 3663, 4096], '146:': [737, 913, 3664, 4097], '905-916Crossref': [738, 914, 3665, 4098], '(1985)': [741, 917, 3668, 4101], 'named': [751], '1The': [753], 'abbreviations': [754], 'used': [755, 2109, 3114], 'are:': [756], 'γH2AX,': [757], 'H2AX;': [761], 'IR,': [762, 1039, 3743, 3825, 4047], 'radiation;': [764], 'top1,': [765, 3513], 'I;': [767], 'AT,': [768], 'telangiectasia;': [770], 'NBS,': [771], 'Nijmegen': [772, 2226], 'breakage': [773, 2227], 'syndrome;': [774], 'ATR,': [775], 'Rad3-related;': [779], 'ATRkd,': [780], 'dead;': [783], 'FITC,': [784, 2667], 'fluorescein': [785], 'isothiocyanate;': [786], 'PBS,': [787, 2620, 2832, 3036], 'phosphate-buffered': [788, 2612], 'saline;': [789], 'MTT,': [790], '3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium': [791], 'bromide;': [792], 'ANOVA,': [793], 'analysis': [794, 2772, 4329], 'variance;': [796], 'PCNA,': [797, 3689], 'proliferating': [798], 'cell': [799, 1927, 2192, 2223, 2604, 2791, 3375, 3398, 4042, 4056], 'nuclear': [800, 2127], 'antigen;': [801], 'DNA-PK,': [802], 'kinase;': [805, 814], 'DNA-PKcs,': [806], 'DNA-PK': [807], 'catalytic': [808, 1523], 'subunit;': [809], 'PIKK,': [810], 'ATM,': [815], 'mutated;': [818], 'MRN,': [819], 'Mre11-Rad50-Nbs1;': [820], 'MEF,': [821], 'fibroblasts;': [824], 'Gy,': [825], 'gray;': [826], 'UCN-01,': [827, 2596, 3913, 3928, 3959], '(8Rogakou': [829, 875], 'rapidly': [857], 'formed': [858, 3678, 3746], 'treated': [861, 2693, 2805, 3247, 3337, 3439, 3823, 3868], 'radiation': [864], '(IR)': [865], 'V(D)J': [869], 'class-switch': [871], 'apoptosis': [874], '9Rogakou': [901], '10Downs': [920], 'J.A.': [921], 'Lowndes': [922], 'N.F.': [923], 'Jackson': [924], 'S.P.': [925, 1832, 1890], 'Nature.': [926, 998], '2000;': [927, 958, 1020, 1107, 1431, 1838, 1896, 2067, 3544, 4147], '408:': [928], '1001-1004Crossref': [929], '(541)': [932], '11Chen': [935], 'H.T.': [936, 973, 1174, 1279], 'Bhandoola': [937], 'A.': [938, 956, 981, 997, 1156, 1166, 1190, 1206, 1271, 1295, 1311, 1339, 1346, 1430, 1774, 1849, 1907, 2091, 2370, 3543, 3704, 3711], 'Difilippantonio': [939, 974, 1183, 1288], 'Zhu': [941], 'Brown': [943], 'Tai': [945], 'X.': [946, 1645], 'Brotz': [949], 'T.M.': [950], 'Ried': [953, 988], 'T.': [954, 989, 993, 1772, 1782, 4270], 'Nussenzweig': [955, 994, 996, 1203, 1205, 1308, 1310, 2476], 'Science.': [957, 1207, 1312, 1650], '290:': [959], '1962-1965Crossref': [960], '(286)': [963], '12Petersen': [966], 'S.': [967, 1155, 1168, 1273, 1345, 1429, 1770, 1784, 3542, 3710], 'Casellas': [968], 'Reina-San-Martin': [970, 1177, 1282], 'B.': [971, 1178, 1283], 'Chen': [972, 1173, 1278], 'Wilson': [976], 'P.C.': [977], 'Hanitsch': [978], 'L.': [979, 1196, 1301, 1641, 1703, 2061, 2563, 4141], 'Celeste': [980], 'Muramatsu': [982], 'M.': [983, 1061, 1102, 1192, 1297, 1768, 1776, 1830, 1888, 2057, 4137], 'Honjo': [992], 'M.C.': [995, 1204, 1309], '414:': [1000], '660-665Crossref': [1001], '(436)': [1004], '13Rogakou': [1007], 'Nieves-Neira': [1009], 'Pommier': [1013, 1401, 1479, 1969, 2062, 3535, 4142, 4275], 'Y.': [1014, 1402, 1413, 1440, 1472, 1480, 1766, 1828, 1835, 1847, 1886, 1893, 1905, 1970, 2063, 3528, 3530, 3536, 4143, 4276], '275:': [1021], '9390-9395Abstract': [1022], '(586)': [1030], 'Because': [1033], 'appears': [1035], 'within': [1036], 'minutes': [1037], 'after': [1038, 2573, 3137, 3946, 4076], 'focus': [1041, 3450, 3613, 3631, 3727, 3794, 3862, 3995, 4224, 4305], 'considered': [1044, 3419], 'sensitive': [1048], 'selective': [1050], 'signal': [1051, 2788], 'existence': [1054], '(14Modesti': [1060], '11:': [1067, 1741], 'R229-R232Abstract': [1068], '(111)': [1076], 'co-localize': [1081], 'including': [1088], 'Rad51,': [1090], 'Brca1': [1092], '(15Paull': [1093], 'T.T.': [1094], 'Yamazaki': [1097], 'V.': [1098, 1180, 1285, 3157], 'Kirchgessner': [1099, 2331], 'C.U.': [1100], 'Gellert': [1101], '10:': [1108], '886-895Abstract': [1109], '(1701)': [1117], 'Recent': [1120], 'studies': [1121], '(16Bassing': [1122], 'C.H.': [1123, 1735], 'Chua': [1124], 'K.F.': [1125], 'Sekiguchi': [1126], 'Suh': [1128], 'H.': [1129, 1421, 1446], 'Whitlow': [1130], 'S.R.': [1131], 'Fleming': [1132], 'J.C.': [1133, 1507], 'Monroe': [1134], 'B.C.': [1135], 'Ciccone': [1136], 'D.N.': [1137], 'Yan': [1138], 'Vlasakova': [1140], 'Livingston': [1142], 'D.M.': [1143, 1423, 1450], 'Ferguson': [1144], 'D.O.': [1145], 'Scully': [1146], 'Alt': [1148], 'F.W.': [1149], 'Proc.': [1150, 1340, 1424, 3537, 3705], 'Natl.': [1151, 1341, 1425, 3538, 3706], 'Acad.': [1152, 1342, 1426, 1836, 1894, 3539, 3707], 'Sci.': [1153, 1343, 1427, 1837, 1895, 3540, 3708], 'U.': [1154, 1344, 1428, 2330, 3541, 3709], '99:': [1158], '8173-8178Crossref': [1159], '(461)': [1162], '17Celeste': [1165], 'Petersen': [1167, 1272], 'Romanienko': [1169, 1274], 'P.J.': [1170, 1275], 'Fernandez-Capetillo': [1171, 1276], 'O.A.': [1176, 1281], 'Coppola': [1179, 1284], 'Meffre': [1181, 1286], 'Olaru': [1189, 1294], 'Eckhaus': [1191, 1296], 'Camerini-Otero': [1193, 1298], 'R.D.': [1194, 1299], 'Tessarollo': [1195, 1300], 'Livak': [1197, 1302], 'F.': [1198, 1303], 'Manova': [1199, 1304], '296:': [1209, 1314], '922-927Crossref': [1210, 1315], '(1141)': [1213, 1318], 'Scholar)': [1215, 1713], 'carried': [1216], 'out': [1217], 'knockout': [1220], 'stem': [1223], 'mice': [1226], 'demonstrated': [1228, 4331], 'involvement': [1230], 'IR.': [1242, 3926, 3949], 'knock-out': [1245, 2170], 'IR': [1250, 1269, 2552, 2592, 3558, 3768, 3857, 3878, 3969, 4077, 4316], 'defective': [1251], 'rejoining': [1256], '53bp1,': [1261], 'Brca1,': [1262], '(17Celeste': [1270], 'An': [1321], 'alternative': [1322], 'source': [1323, 2556], 'conversion': [1330], 'single-strand': [1332, 1356, 1396], 'advancing': [1335], 'forks': [1337], '(18Kuzminov': [1338], '98:': [1348], '8241-8246Crossref': [1349], '(297)': [1352], 'produced': [1360], 'variety': [1363], 'exogenous': [1365], 'endogenous': [1367], 'action': [1373], '(top1)': [1378], 'containing': [1381, 2352, 2390, 2635, 2949, 3125], 'base': [1382], 'damages': [1383], '(abasic': [1384], 'sites,': [1385], 'mismatches,': [1386], 'oxidized': [1387], 'bases,': [1388], 'carcinogenic': [1389], 'adducts,': [1390], 'UV': [1392], 'lesions)': [1393], 'preexisting': [1395], '(discover.nci.nih.gov/pommier/topo1.htm)': [1398, 1878], '(19Pourquier': [1399], 'P.': [1400, 1417, 1468, 3526], 'Adv.': [1403, 1852, 1910], 'Cancer': [1404, 1481, 1704, 1814, 1971, 1984, 2098, 2410, 4277, 4403], '80:': [1407], '189-216Crossref': [1408], '20Pommier': [1412], 'Kohlhagen': [1414, 1441, 3533], 'Pourquier': [1416], 'Sayer': [1418, 1447], 'J.M.': [1419, 1448, 1966], 'Kroth': [1420, 1445], 'Jerina': [1422, 1449], '97:': [1432, 3545], '2040-2045Crossref': [1433], '(65)': [1436], '21Pommier': [1439], 'Laco': [1443], 'G.S.': [1444], '277:': [1455], '13666-13672Abstract': [1456], '(32)': [1464], '22Pourquier': [1467], 'Waltman': [1469], 'J.L.': [1470, 1478], 'Urasaki': [1471, 3529], 'Loktionova': [1473], 'N.A.': [1474], 'Pegg': [1475], 'A.E.': [1476], 'Nitiss': [1477], '61:': [1484], '53-58PubMed': [1485], 'Top1': [1488, 1659, 3426], 'ubiquitous': [1491], 'enzyme': [1492, 1532], 'regulates': [1494], 'topological': [1496], 'state': [1497], '(23Wang': [1506], 'Mol.': [1510, 2064, 2077, 4144], 'Cell.': [1511, 2065, 2078, 4145], '430-440Crossref': [1515], '(1916)': [1518], 'top1': [1522, 1552, 1632, 1682, 1800, 1924, 2023], 'cycle': [1524, 1928, 4057], 'summarized': [1527], 'follows.': [1529], '1)': [1530], 'binds': [1533], 'duplex': [1535], '(Fig.': [1537, 1585, 1607, 1638, 1876, 2014, 3456, 3471, 3500, 3734, 3753, 3786, 3839, 4015, 4079, 4171, 4188, 4212, 4317, 4339], '1A).': [1538], '2)': [1539], 'It': [1540], 'cleaves': [1541], 'one': [1542, 2652], 'trans-esterification': [1547], 'reaction': [1548], 'tyrosine-hydroxyl': [1553], 'group': [1554], 'becomes': [1555], 'covalently': [1556], 'linked': [1557], '3′-phosphate': [1560], 'phosphodiester': [1564], 'bond': [1565], 'generate': [1567], '5′-hydroxyl': [1569, 1625], 'terminus.': [1571], 'intermediate': [1574], 'commonly': [1576], 'referred': [1577], '(or': [1582], 'cleavable)': [1583], 'complex': [1584], '1B).': [1586, 1608], '3)': [1587], 'supercoiling': [1589], 'relaxed': [1591], 'controlled': [1593], 'rotation': [1594], '5′-end': [1597, 2036], 'broken': [1600], 'intact': [1604], '4)': [1609], 'After': [1610, 2584, 3180, 3259], 'relaxation': [1612], 'complete,': [1614], 'cleaved': [1616, 2039], 'religated': [1619], 'nucleophilic': [1621], 'attack': [1622], 'dissociation': [1629], 'tyrosyl': [1633], 'residue': [1634], '3′-end': [1637], '1A)': [1639], '(24Stewart': [1640], 'Redinbo': [1642], 'M.R.': [1643], 'Qiu': [1644], 'Hol': [1646], 'W.G.J.': [1647], 'Champoux': [1648], 'J.J.': [1649], '279:': [1652], '1534-1541Crossref': [1653], '(622)': [1656], 'generally': [1663, 3634], 'widely': [1664], 'distributed': [1665, 4051], 'genome': [1668], 'normally': [1670], 'transient.': [1672], 'Camptothecin': [1673, 1862], 'derivatives': [1676, 1865], '(irinotecan': [1677], 'topotecan)': [1679], 'specific': [1681, 4114], 'inhibitors.': [1683], 'Irinotecan': [1684], 'recently': [1686], 'approved': [1688, 1718], 'FDA': [1691], '(Food': [1692], '&': [1693], 'Drug': [1694, 2404], 'Administration)': [1695], 'treatment': [1698, 1721, 1759, 2585, 3023, 3769, 3922, 3938, 4078], 'colon': [1700, 2175, 3434], 'cancers': [1701, 1724, 1762], '(25Stucky-Marshall': [1702], 'Nurs.': [1705], '212-219Crossref': [1708], '(10)': [1711], 'topotecan': [1715], 'ovarian': [1723], '(26Barnett': [1725], 'A.A.': [1726, 2055, 4135], 'Lancet.': [1727], '1996;': [1728], '347:': [1729], '1613Crossref': [1730], '27Takimoto': [1734], 'Arbuck': [1736], 'S.G.': [1737], 'Oncology': [1738], '(Huntington).': [1739], '1997;': [1740, 4279], '1635-1655PubMed': [1742], 'Moreover,': [1745], 'recent': [1747], 'clinical': [1748, 4256], 'study': [1749], 'revealed': [1750], 'irinotecan': [1752], 'superior': [1754], 'etoposide': [1756], 'lung': [1761], '(28Noda': [1763], 'Nishiwaki': [1765], 'Kawahara': [1767], 'Negoro': [1769], 'Sugiura': [1771], 'Yokoyama': [1773], 'Fukuoka': [1775], 'Mori': [1777], 'Watanabe': [1779], 'Tamura': [1781], 'Yamamoto': [1783], 'Saijo': [1785], 'N.': [1786, 1787, 1834, 1892], 'Engl.': [1788], 'Med.': [1790], '346:': [1792], '85-91Crossref': [1793], '(1287)': [1796], 'Therefore,': [1799], 'important': [1803], 'target': [1805], 'cancer': [1807], 'chemotherapy': [1808], '(29Garcia-Carbonero': [1809], 'Supko': [1811], 'J.G.': [1812], 'Clin.': [1813], '8:': [1817], '641-661PubMed': [1818], '30Liu': [1821], 'L.F.': [1822, 1880, 1983, 2097], 'Desai': [1823, 1881], 'S.D.': [1824, 1882, 3364], 'Li': [1825, 1883], 'T.K.': [1826, 1884], 'Mao': [1827, 1885], 'Sun': [1829, 1887], 'Sim': [1831, 1889], 'Ann.': [1833, 1891], '922:': [1839, 1897], '1-10Crossref': [1840, 1898], '(429)': [1843, 1901], '31Pommier': [1846, 1904], 'Tanizawa': [1848, 1906], 'Kohn': [1850, 1908, 4273], 'K.W.': [1851, 1909, 4274], 'Pharmacol.': [1853, 1911], '29B:': [1855, 1913], '73-92Crossref': [1856, 1914], '(81)': [1859, 1917], 'trap': [1866], 'top1-DNA': [1867], 'inhibiting': [1871], 'religation': [1874], 'step': [1875], '1C)': [1877], '(30Liu': [1879], 'Despite': [1920], 'abundance': [1922], 'quiescent': [1931], 'cytotoxicity': [1934, 1960], 'remarkably': [1938], 'limited': [1939], 'replicating': [1941, 3699], 'cells.': [1942, 2172, 3351, 3564, 3802, 3973], 'For': [1943, 4017], 'instance,': [1944], 'when': [1945, 2804, 3017, 3432], 'pretreated': [1948, 3910], 'polymerase': [1952], 'inhibitor,': [1953], 'aphidicolin,': [1954, 2597, 4112], 'they': [1955, 3018, 3039], 'protected': [1957], 'camptothecins': [1962, 2002], '(32Holm': [1963], 'Covey': [1965], 'Kerrigan': [1967], '1989;': [1973, 1986], '49:': [1974, 1987], '6365-6368PubMed': [1975], '33Hsiang': [1978], 'Y.H.': [1979], 'Lihou': [1980], 'M.G.': [1981], 'Liu': [1982, 2096], '5077-5082PubMed': [1988], 'dependence': [1993], 'lethal': [1998], 'explained': [2005], '1D).': [2015], 'When': [2016, 3411], 'proceeds': [2020], 'toward': [2021], 'complex,': [2025], 'extension': [2027], 'leading': [2030], 'blocked': [2033, 2632, 2935, 3161], 'template': [2041], 'runoff,': [2045], '(34Strumberg': [2052, 4132], 'Pilon': [2054, 4134], 'Smith': [2056, 4136], 'Hickey': [2058, 4138], 'Malkas': [2060, 4140], '20:': [2068, 4148], '3977-3987Crossref': [2069, 4149], '(287)': [2072, 4152], '35Snapka': [2075], 'R.M.': [2076], '1986;': [2080], '6:': [2081], '4221-4227Crossref': [2082], '(109)': [2085], '36Tsao': [2088], 'Y.P.': [2089], 'Russo': [2090], 'Nyamuswa': [2092], 'Silber': [2094], '1993;': [2100], '53:': [2101], '5908-5914PubMed': [2102], 'this': [2106], 'study,': [2107], 'investigate': [2112], 'whether': [2113], 'concentration': [2125, 2885, 3111, 3321, 3402, 3455], 'We': [2129, 4059, 4104, 4373], 'studied': [2131, 2167], 'upstream': [2133], 'implicated': [2135], 'relationship': [2143, 3992], 'between': [2144, 3372, 3395, 3993], 'proteins,': [2155], 'Nbs1.': [2159], 'Finally,': [2160], 'functional': [2162], 'role': [2163], 'was': [2166, 2233, 2454, 2472, 2531, 2738, 2894, 2934, 3091, 3107, 3160, 3209, 3271, 3282, 3289, 3303, 3325, 3377, 3404, 3414, 3418, 3555, 3608, 3615, 3633, 3729, 3796, 3831, 3931, 4000, 4029, 4049], 'Culture—Human': [2174], 'HT29': [2177], 'were': [2181, 2207, 2244, 2280, 2296, 2325, 2340, 2365, 2377, 2400, 2416, 2421, 2443, 2464, 2489, 2514, 2545, 2569, 2579, 2606, 2692, 2706, 2769, 2792, 2799, 2810, 2828, 2845, 2861, 2876, 2921, 2969, 3002, 3012, 3019, 3028, 3040, 3131, 3146, 3191, 3229, 3246, 3353, 3358, 3438, 3447, 3772, 3776, 3808, 3815, 3909, 3976, 4074], 'obtained': [2182, 2208], 'Developmental': [2185], 'Therapeutics': [2186], 'Program,': [2187], 'NCI.': [2188, 2412], 'SV40-transformed': [2190, 2221], 'fibroblast': [2191, 2222], 'lines': [2193, 3376, 3399], 'normal': [2195], 'individual': [2196], '(GM00637)': [2197], '(AT)': [2203], 'homozygous': [2204, 2230], 'patient': [2205, 2231], '(GM05849)': [2206], 'Dr.': [2210, 2328, 2368, 2475], 'Michael': [2211, 2286], 'Kastan': [2212], '(St.': [2213], 'Jude': [2214], "Children's": [2215], 'Research': [2216, 2240, 2493], 'Hospital,': [2217], 'Memphis,': [2218], 'TN).': [2219], 'line': [2224], 'syndrome': [2228], '(NBS)': [2229], '(GM15989)': [2232], 'purchased': [2234, 2417, 2444, 2455, 2465, 2490, 2515, 2532], 'Coriell': [2236], 'Institute': [2237], 'Medical': [2239], '(Camden,': [2241], 'NJ).': [2242], 'They': [2243, 2295], 'grown': [2245, 2297, 2341, 2580, 2800, 3013], '37': [2247, 2316, 2601], '°C': [2248, 2317, 2627, 2818], 'presence': [2251, 3886], '5%': [2253, 2319, 2639, 2950, 3163], 'CO2': [2254], "Dulbecco's": [2256, 2380], "Eagle's": [2258, 2382], 'medium': [2259, 2301, 2345, 2383, 2433, 2710, 3281, 3935], 'supplemented': [2260, 2302, 2346, 2384], '10%': [2262, 2304, 2348, 2386], 'fetal': [2263, 2305, 2349, 2387], 'bovine': [2264, 2306, 2350, 2388], 'serum': [2265, 2351, 2389, 2641], '(Invitrogen),': [2266], '100': [2267, 2271, 2308, 2312, 3080, 3285, 3902], 'units/ml': [2268, 2309, 2696], 'penicillin,': [2269, 2310], 'μg/ml': [2272, 2313, 2354, 2392, 3078], 'streptomycin.': [2273], 'P388': [2274], 'P388/CPT45': [2276], 'leukemia': [2278, 3523], 'kind': [2282], 'gift': [2283], 'Drs.': [2285], 'Mattern': [2288], 'Randal': [2290], 'Johnson': [2292], '(SmithKline': [2293], 'Beecham).': [2294], 'RPMI': [2299, 2343], '1640': [2300, 2344], 'serum,': [2307], 'streptomycin': [2314], 'CO2.': [2320], 'M059J/Fus1': [2321], 'M059J/Fus9': [2323], 'donated': [2326, 2366, 2473], 'Cordula': [2329], '(Stanford': [2332], 'University': [2333], 'School': [2334], 'Medicine,': [2336], 'Stanford,': [2337], 'CA)': [2338, 2716], '400': [2353, 2391], 'G418': [2355], '(Invitrogen).': [2356], 'Ataxia': [2357], 'Rad3-related': [2360], 'dead': [2362], '(ATRkd)': [2363], 'William': [2369], 'Cliby': [2371], '(Mayo': [2372], 'Clinic,': [2373], 'Rochester,': [2374], 'MN)': [2375], 'incubated': [2378, 2650, 2664, 2975, 3041, 3192, 3242], 'G418.': [2393], 'Drugs,': [2394], 'Chemicals,': [2395], 'Antibodies—Camptothecin': [2397], 'UCN-01': [2399, 3845, 3897, 4236, 4290, 4301, 4333], 'provided': [2401], 'Synthesis': [2405], 'Chemistry': [2406], 'Branch,': [2407], 'Division': [2408], 'Treatment,': [2411], 'Aphidicolin': [2413], 'wortmannin': [2415, 2599, 3848], 'Sigma.': [2419], 'Aliquots': [2420], 'stored': [2422, 3119], 'frozen': [2423], '10': [2425, 2695, 2890, 3263, 3643], 'mm': [2426, 2939, 2944, 3054, 3057, 3060, 3063, 3069, 3074, 3084], 'Me2SO': [2428, 3288], 'diluted': [2430], 'further': [2431, 4001], 'immediately': [2434, 3115], 'prior': [2435, 2956, 3169, 3919], 'each': [2437, 2790, 3239, 3275, 3292, 3298, 3320, 3401], 'experiment.': [2438], 'Anti-γH2AX': [2439, 2450], 'monoclonal': [2441], 'antibody': [2442, 2453, 2471, 2526, 2679, 2761, 2963, 2980, 3174, 3195], 'Upstate': [2446], 'Biotechnology': [2447], '(Altham,': [2448], 'MA).': [2449, 2780, 2931], 'rabbit': [2451], 'polyclonal': [2452], 'Trevigen,': [2457], '(Gaithersburg,': [2458], 'MD).': [2459, 2483], 'Anti-Mre11': [2460], 'Rad50': [2462], 'antibodies': [2463, 2488, 2507, 2656], 'Novus': [2467], '(Littleton,': [2468], 'CO).': [2469], 'Anti-Nbs1': [2470], '(NCI,': [2477], 'National': [2478], 'Institutes': [2479], 'Health,': [2481], 'Bethesda,': [2482], 'FITC-conjugated': [2484, 2759], 'anti-mouse': [2485, 2503, 2524, 2676, 2979], 'anti-rabbit': [2487, 2505, 2674], 'Oncogene': [2492], 'Products': [2494], '(Oncogene': [2495], 'Science': [2496], 'Inc.,': [2497, 2714], 'San': [2498, 2915], 'Diego,': [2499, 2916], 'CA).': [2500, 2917, 3314], 'second': [2502, 2523, 2678, 2760], 'or': [2504, 2512, 2541, 2591, 2594, 2598, 2653, 2670, 2675, 2733, 3118, 3249, 3767, 3856, 3877, 3885, 3901, 3914, 3925, 3929, 3943, 3968], 'Ig': [2506, 2525, 2677], 'conjugated': [2508, 2527], 'AlexaFluor': [2510, 2668, 2671], '488': [2511], '546': [2513], 'Molecular': [2517, 3310], 'Probes,': [2518], 'Inc.': [2519], '(Eugene,': [2520], 'OR).': [2521], 'horseradish': [2529, 2977], 'peroxidase': [2530], 'Amersham': [2534], 'Biosciences.': [2535], 'IR—Cells': [2536], 'growing': [2537], 'T75': [2539], 'flask': [2540], 'chamber': [2543, 2582], 'slides': [2544, 2691, 2705, 3761], 'indicated': [2549, 2587, 3252], 'dose': [2550], '137Cs': [2555], 'Mark': [2559], 'irradiator': [2561], '(J.': [2562], 'Shepherd': [2564], 'Associates).': [2566], 'analyses': [2568, 3953, 4196], 'performed': [2570, 3354, 3682], '30': [2571, 3045, 3944], 'min': [2572, 2955, 3046, 3101, 3186, 3918, 3945], 'irradiation.': [2574], 'Laser': [2575, 2744], 'Scanning': [2576, 2745], 'Confocal': [2577], 'Microscopy—Cells': [2578], 'slides.': [2583], 'doses': [2588], 'without': [2595, 3248], '°C,': [2602], 'preparations': [2605], 'fixed': [2607], '2%': [2609], 'paraformaldehyde': [2610], 'saline': [2613], '(PBS)': [2614], '5': [2616, 3077, 3185], 'min,': [2617, 2630], 'washed': [2618, 2687, 2829, 2970, 3033], 'permeabilized': [2621], '100%': [2623, 2855, 2864], 'methanol': [2624], '-20': [2626], '20': [2629, 3126, 3156], 'washed,': [2631, 2663], 'PBS': [2634], '1%': [2636], 'BSA': [2637], 'goat': [2640, 2673], '(Jackson': [2642], 'Immunolaboratories,': [2643], 'West': [2644, 2992], 'Grove,': [2645], 'PA)': [2646], '1': [2648, 2684, 3062, 3073, 3153, 3167, 3443, 3888], 'h,': [2649, 2662, 2685, 3444], 'two': [2654, 3374, 3397], 'first': [2655, 2755, 3571, 3598], '800-fold': [2658], 'dilution': [2659, 2682], '2': [2661, 2965, 3059, 3083, 3178], '484,': [2669], '546-conjugated': [2672], '200-fold': [2681], 'PBS.': [2689], 'Some': [2690], 'ribonuclease': [2697], '(Sigma)': [2698], 'stained': [2700, 2749], 'propidium': [2702, 2751], 'iodide.': [2703], 'mounted': [2707], 'mounting': [2709], '(Vectashield,': [2711], 'Vector': [2712], 'Laboratories,': [2713], 'Burlingame,': [2715], 'viewed': [2718], 'PCM2000': [2721], 'laser': [2722, 2774, 4012], 'scanning': [2723, 2775, 4013], 'confocal': [2724], 'microscope': [2725], '(Nikon': [2726], 'Co.,': [2727], 'Tokyo,': [2728], 'Japan)': [2729], 'using': [2730, 2987, 3202, 4011], '×40': [2732], '×100': [2734], 'objectives.': [2735], 'projection': [2737], 'saved': [2739], 'BMP': [2742], 'file.': [2743], 'Cytometry—Slides': [2746], 'iodide,': [2752], 'anti-γH2AX': [2754, 2962], 'antibody,': [2756], 'prepared': [2762], 'protocol': [2765], 'described': [2767, 3980], 'above': [2768], 'subjected': [2770, 3020], 'cytometry': [2776, 4014], '(LSC®,': [2777], 'CompuCute,': [2778], 'Cambridge,': [2779], 'content': [2783], 'intensity': [2785], 'FITC': [2787], 'determined.': [2793], 'Western': [2794, 3007, 3487, 3951, 4194, 4327], 'Blot': [2795], 'Analysis': [2796, 3009], 'γH2AX—Cells': [2798], '50–80%': [2802, 3015], 'confluence': [2803], 'different': [2807, 3025, 3339], 'agents.': [2808, 3026], 'Cells': [2809, 3027, 3223, 3908], 'scraped': [2811], 'pelleted': [2813, 2846], 'centrifugation': [2815, 3094], '0': [2817], '1,000': [2820, 3235], '×': [2821, 2842, 2872, 3097], 'g': [2822, 3098, 3483, 4320], '15': [2824, 3100, 3917], 'min.': [2825], 'pellets': [2827, 2860, 2875], 'twice': [2830, 3034], 'homogenized': [2833], '0.2': [2835], 'n': [2836], 'H2SO4,': [2837], 'centrifuged': [2839, 2868], '13,000': [2841, 2871], 'g.': [2843, 2873], 'Histones': [2844], 'supernatant': [2849, 3106], 'adding': [2851], '0.25': [2852], 'volume': [2853], '(w/v)': [2856], 'trichloroacetic': [2857], 'acid.': [2858], 'suspended': [2862], 'ethanol': [2865], 'overnight': [2866], 'again': [2869], 'dissolved': [2877], 'ultrapure': [2879], 'water,': [2880], 'evaluated': [2882, 3108], '(Bio-Rad).': [2886], 'Aliquot': [2887], 'corresponding': [2888, 3762], 'μg': [2891, 3127], 'boiled': [2895, 3139], 'SDS': [2897, 2901, 3141], 'sample': [2898, 2902, 3142], 'buffer': [2899, 2903, 3049, 3143], '(Tris-glycine': [2900], '(twice),': [2904], 'Invitrogen)': [2905], 'loaded': [2907], 'onto': [2908], '4–20%': [2910], 'Tris-Glycin': [2911, 3134], 'precast': [2912, 3135], 'gel': [2913], '(Novex,': [2914], 'separated': [2919], 'transferred': [2922, 3148], 'polyvinylidene': [2925], 'difluoride': [2926], 'membrane': [2927, 2933, 3159], '(Immobilon-P,': [2928], 'Millipore,': [2929], 'Bedford,': [2930], 'TBST': [2937, 2972, 3183], '(10': [2938, 3879], 'Tris-Cl,': [2940], 'pH': [2941, 3071], '7.4,': [2942, 3072], '200': [2943], 'NaCl,': [2945, 3058], '0.1%': [2946], 'Tween': [2947], '20)': [2948], 'nonfat': [2951, 3164], 'milk': [2952, 3165], '60': [2954], 'incubation': [2958, 3171], '50': [2960, 3068], 'ng/ml': [2961], 'h.': [2966, 3179, 3258], 'blots': [2968], 'then': [2974, 3038, 3145], 'peroxidase-conjugated': [2978], '(1/1,000': [2981, 3196], 'dilution)': [2982, 3176, 3197], 'visualized': [2984, 3199], 'chemiluminescence': [2986, 3201], 'Supersignal': [2989, 3204], 'kit': [2990], '(SuperSignal®': [2991], 'Pico': [2993], 'chemiluminescent': [2994], 'substrate,': [2995], 'Pierce).': [2996], 'All': [2997], 'presented': [3000, 3207], 'data': [3001], 'confirmed': [3003, 3210, 3489, 4197], 'independent': [3005, 3212], 'experiments.': [3006, 3213], 'Blotting': [3008], 'Nbs1—Cells': [3011], 'confluency': [3016], 'harvested': [3029], 'scrape': [3031], 'ice': [3043], 'lysis': [3048], '(0.3%': [3050], 'Nonidet': [3051], 'P-40,': [3052], '25': [3053], 'NaF,': [3055], '150': [3056], 'EGTA,': [3061], 'EDTA,': [3064], '0.2%': [3065], 'Triton': [3066], 'X-100,': [3067], 'Tris-HCl,': [3070], 'phenylmethylsulfonyl': [3075], 'fluoride,': [3076], 'aprotinin,': [3079], 'μm': [3081, 3889, 3896, 3903], 'leupeptin,': [3082], 'AEBSF': [3085], '(4-(2-aminoethyl)benzenesulfonyl': [3086], 'fluoride': [3087], 'hydrochloride)).': [3088], 'debris': [3090], 'removed': [3092], '12,000': [3096], '4': [3103, 3277], '°C.': [3104, 3122], 'either': [3113], 'assays': [3117], '-70': [3121], 'lysates': [3124], 'electrophoresed': [3132], 'gels': [3136], 'being': [3138], 'electrophoretically': [3147], 'Immobilon-P': [3150], 'membranes': [3151, 3190], 'h': [3154, 3168, 3278], 'anti-Nbs1': [3173], '(1/10,000': [3175], 'washing': [3181], 'times,': [3188], 'secondary': [3194], 'kit.': [3205], 'result': [3208], 'MTT': [3214, 3266], 'Assay': [3215], 'Cellular': [3217], 'Response': [3218, 4245], 'H2AX+/+': [3220], 'Camptothecin—H2AX+/+': [3225], 'seeded': [3230], 'into': [3231, 3778], '96-well': [3232], 'microplates': [3233], 'cells/90': [3236], 'μl': [3237, 3264, 3286], 'overnight.': [3243], 'concentrations': [3253, 3340], '72': [3257], '72-h': [3261], 'incubation,': [3262], 'solution': [3267], '(5': [3268], 'mg/ml,': [3269], 'Sigma)': [3270], 'added': [3272, 3290], 'well.': [3276, 3293], 'later,': [3279], 'aspirated': [3283], 'optical': [3295, 3333, 3346], 'density': [3296, 3334, 3347], '(wavelength': [3300], '520': [3301], 'nm)': [3302], 'measured': [3304], 'microplate': [3307], 'reader': [3308], '(Emax,': [3309], 'Devices': [3311], 'Corp.,': [3312], 'Sunnyvale,': [3313], 'survival': [3316, 3393], 'drug': [3324, 4254], 'expressed': [3326, 3359], 'percentage': [3329, 3827], 'ratio': [3330], 'mean': [3345, 3362], 'untreated': [3350], 'Measurements': [3352], 'triplicate.': [3356], 'Data': [3357], '±': [3363], 'statistical': [3366], 'difference': [3367, 3417], 'overall': [3369], 'responses': [3371], 'assessed': [3378, 3405], 'two-way': [3381], 'ANOVA': [3382], 'followed': [3383], "Scheffe's": [3386], 'multiple': [3387], 'comparison': [3388], 'test.': [3389, 3410], 'Difference': [3390], 'ratios': [3394], 'point': [3403], "Student's": [3408], 't': [3409], 'p': [3412], 'value': [3413], '<0.05,': [3415], 'statistically': [3420], 'significant.': [3421], 'Production': [3422], 'Cleavage': [3427], 'Complex—Fig.': [3428], '2A': [3429, 3625], 'shows': [3430, 3508, 4157, 4288], 'observed.': [3448], 'increased': [3452, 4360], '2A,': [3457, 3472], 'compare': [3458, 3473, 4081, 4173, 4190, 4319], 'a,': [3459], 'b,': [3460], 'd,': [3461], 'f)': [3463], 'increasing': [3466], 'time': [3468, 3572], 'exposure': [3470, 3947], 'b': [3474, 4214], 'c': [3476], 'd': [3478], 'e)': [3480], '(see': [3481, 4371], 'panels': [3482], 'Fig.': [3485, 3505, 4155, 4284], '2A).': [3486], 'blotting': [3488, 4195, 4328], 'time-dependent': [3491, 3587], 'concentration-dependent': [3493], 'generation': [3494, 4336], 'camptothecin-treated': [3498, 3622, 3724, 4130, 4205, 4308], '2B,': [3501], 'b).': [3504, 3756, 4341], '2C': [3506], 'because': [3514, 3690, 4357], 'failed': [3516, 4065], 'top1-deficient': [3521, 3561], '(37Pourquier': [3525], 'Takebayashi': [3527], 'Gioffre': [3531], '1885-1890Crossref': [3546], '(96)': [3549], 'By': [3552, 3628, 3819, 4044, 4177], 'contrast,': [3553, 3629, 3820, 4045, 4178], 'generated': [3556], 'both': [3560, 3686, 3747], 'top1-proficient': [3563], 'Together,': [3565], 'these': [3566, 3759, 3804], 'indicate': [3568, 4219], 'top1-mediated': [3574], 'dose-dependent': [3585], 'manners.': [3588], 'Top1-mediated': [3589, 4247], 'Foci': [3591], 'Are': [3592], 'Attributed': [3593], 'Replication-mediated': [3595, 4249], 'Damage—The': [3597], 'suggestion': [3599], 'replication-dependent': [3602, 4229], 'induction': [3603, 3964], 'observation': [3610], 'restricted': [3616, 3730], 'fraction': [3619, 3674], '(Figs.': [3624, 3645], '3A).': [3627], 'observed': [3635, 3797, 4075], 'all': [3637, 4053], 'irradiated': [3641], 'Gy': [3644], '3A': [3646], '4A)': [3648], 'reported': [3650], 'previously': [3651], 'To': [3671, 3757], 'determine': [3672], 'foci,': [3680, 4070], 'double': [3683], 'staining': [3684], 'PCNA': [3691], 'levels': [3692], 'highest': [3697, 4024], '(38Celis': [3701], 'J.E.': [3702], 'Celis': [3703], '1985;': [3712], '82:': [3713], '3262-3266Crossref': [3714], '(608)': [3717], 'case': [3722, 3741, 3790], 'PCNA-positive': [3732, 3749, 3834], '3A,': [3735, 3754], 'panel': [3736, 3755], 'a),': [3737], 'PCNA-negative': [3751, 3813, 3836], 'quantify': [3758], 'results,': [3760], '(611': [3765], 'cells)': [3766, 3771, 4370], '(605': [3770], 'scored': [3773], 'classified': [3777], 'groups:': [3780], 'PCNA-/γH2AX-,': [3781], 'PCNA-/γH2AX+,': [3782], 'PCNA+/γH2AX-,': [3783], 'PCNA+/γH2AX+': [3785], '3B).': [3787], '51%': [3799], 'γH2AX-positive': [3805, 3829], '92%': [3807], 'PCNA-positive.': [3810], 'Conversely,': [3811], '86%': [3812], 'negative': [3816], 'similar': [3832], '(94%)': [3838], '3B).Fig.': [3840], '4Effects': [3841], '(APH),': [3844], '(7-hydroxystaurosporine),': [3846], '(Wort)': [3849], '(CPT)': [3855], 'cells.A,': [3860], '(green)': [3864], 'CPT': [3870, 3924], '(1': [3871], 'μm,': [3872], '3': [3874], 'h)': [3875, 3942], '(e)': [3876], 'Gy)': [3880], '(i)': [3881], 'absence': [3884, 4363], '(APH)': [3891], '(f': [3892], 'j).': [3894], '0.1': [3895], '(g': [3898], 'k),': [3900], 'Wort': [3904, 3915, 3930, 3961], '(h': [3905], 'l).': [3907], 'APH,': [3912, 3927, 3958], 'kept': [3932], '(3': [3941], 'B,': [3950], 'blot': [3952], 'effects': [3956], '(b)': [3967], '(c)': [3970], 'Treatment': [3974], 'schedules': [3975], 'same': [3978], 'A.View': [3982], 'Large': [3983], 'Image': [3984], 'Figure': [3985], 'ViewerDownload': [3986], 'Hi-res': [3987], 'image': [3988], 'Download': [3989], '(PPT)': [3990], 'examined': [4002], 'comparing': [4004], 'contents': [4010], '3C).': [4016], 'S-phase': [4021, 4260], 'had': [4022], 'contents,': [4026], 'lowest': [4030], 'G1': [4036], 'G2/M': [4038], 'phases': [4039], 'cycle.': [4043], 'equally': [4050], 'phases.': [4058], 'mitotic': [4063], '3D,': [4080], 'b)': [4084], 'next': [4105, 4374], 'determined': [4106, 4375], 'effect': [4108, 4377], 'pretreatment': [4110, 4159, 4299], 'polymerases': [4118], 'blocks': [4120], '4A': [4156, 4285], 'completely': [4162], '4A,': [4172, 4189, 4318], 'f': [4174], 'e).': [4176], 'IR-induced': [4179], 'remained': [4182], 'clearly': [4183], 'detectable': [4184], 'aphidicolin-treated': [4186], 'j': [4191], 'i).': [4193, 4326], 'inhibition': [4198], 'IR-treated': [4210], '4B,': [4213, 4340], 'c).': [4216], 'induces': [4222], 'manner.': [4230], 'Cycle': [4233], 'Checkpoint': [4234], 'Modulators,': [4235], 'Wortmannin,': [4238], 'Affect': [4239], 'Formation': [4241], 'Damage—UCN-01,': [4251], 'anti-cancer': [4253], 'trials,': [4257], 'abrogates': [4258], '(39Shao': [4265], 'R.G.': [4266], 'Cao': [4267], 'C.X.': [4268], 'Shimizu': [4269], "O'Connor": [4271], 'P.M.': [4272], '57:': [4280], '4029-4035PubMed': [4281], '(panel': [4286], 'c)': [4287], 'itself': [4292], 'did': [4293], 'e': [4322], 'k': [4324], 'consistent': [4345], 'findings': [4348], 'replication-dependent,': [4356], '(i.e.': [4367], 'UCN-01-treated': [4369], '"Discussion").': [4372], 'wortmannin,': [4379], 'non-competitive': [4381], 'irreversible': [4383], '(PIKKs)': [4390], '(40Sarkaria': [4391], 'J.N.': [4392], 'Tibbetts': [4393], 'R.S.': [4394], 'Busby': [4395], 'E.C.': [4396], 'Kennedy': [4397], 'A.P.': [4398], 'Hill': [4399], 'D.E.': [4400], 'Abraham': [4401], 'R.T.': [4402], '58:': [4406], '4375-4382PubMed': [4407]}, 'cited_by_api_url': 'https://api.openalex.org/works?filter=cites:W2119186872', 'counts_by_year': [{'year': 2024, 'cited_by_count': 4}, {'year': 2023, 'cited_by_count': 19}, {'year': 2022, 'cited_by_count': 10}, {'year': 2021, 'cited_by_count': 17}, {'year': 2020, 'cited_by_count': 8}, {'year': 2019, 'cited_by_count': 16}, {'year': 2018, 'cited_by_count': 8}, {'year': 2017, 'cited_by_count': 5}, {'year': 2016, 'cited_by_count': 10}, {'year': 2015, 'cited_by_count': 23}, {'year': 2014, 'cited_by_count': 20}, {'year': 2013, 'cited_by_count': 17}, {'year': 2012, 'cited_by_count': 24}], 'updated_date': '2024-12-14T02:53:18.708678', 'created_date': '2016-06-24'}
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