Ku DNA end-binding protein modulates homologous repair of double-strand breaks in mammalian cells.
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 Ku-modulated two-ended versus one-ended chromosome break model is presented to explain these results.
Pierce
A J
AJ
Cell Biology Program, Memorial Sloan-Kettering Cancer Center, and Cornell University Graduate School of Medical Sciences, New York, New York 10021, USA.
Hu
P
P
Han
M
M
Ellis
N
N
Jasin
M
M
D000818:Animals; D034961:Antigens, Nuclear; D002460:Cell Line; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics*; D004249:DNA Damage; D004265:DNA Helicases; D017931:DNA Primers / Q000737:chemistry; D004260:DNA Repair / Q000235:genetics*; D051747:DNA-Activated Protein Kinase; D004268:DNA-Binding Proteins / Q000235:genetics*; D018390:Gene Targeting; D006801:Humans; D000072200:Ku Autoantigen; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D009687:Nuclear Proteins / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011995:Recombination, Genetic; D012854:Sister Chromatid Exchange / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics*
D034961:Antigens, Nuclear; D017931:DNA Primers; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; D004247:DNA; D051747:DNA-Activated Protein Kinase; C497264:Prkdc protein, mouse; D004265:DNA Helicases; C106893:XRCC5 protein, human; C000606509:Xrcc6 protein, human; C000606510:Xrcc6 protein, mouse; D000072200:Ku Autoantigen