Ku DNA end-binding protein modulates homologous repair of double-strand breaks in mammalian cells

被引:443
作者
Pierce, AJ
Hu, P
Han, MG
Ellis, N
Jasin, M
机构
[1] Mem Sloan Kettering Canc Ctr, Cell Biol Program, New York, NY 10021 USA
[2] Cornell Univ, Grad Sch Med Sci, New York, NY 10021 USA
关键词
homologous recombination; DNA double-strand break; nonhomologous end-joining; Ku protein; DNA-PK; sister-chromatid exchange; gene targeting;
D O I
10.1101/gad.946401
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Chromosomal double-strand breaks (DSBs) in mammalian cells are repaired by either homology-directed repair (HDR), using a homologous sequence as a repair template, or nonhomologous end-joining (NHEJ), which often involves sequence alterations at the DSB site. To characterize the interrelationship of these two pathways, we analyzed HDR of a DSB in cells deficient for NHEJ components. We find that the HDR frequency is enhanced in Ku70(-/-), XRCC4(-/-), and DNA-PKcs(-/-) cells, with the increase being particularly striking in Ku70(-/-) cells. Neither sister-chromatid exchange nor gene-targeting frequencies show a dependence on these NHEJ proteins. A Ru-modulated two-ended versus one-ended chromosome break model is presented to explain these results.
引用
收藏
页码:3237 / 3242
页数:6
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