Ku DNA end-binding protein modulates homologous repair of double-strand breaks in mammalian cells.
Journal:
Genes Dev. 2001 DecAuthors:
Pierce AJ, Hu P, Han M, Ellis N, Jasin M
Abstract
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 be
...[more]ing 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.[less]
Mesh Headings:
Animals, Antigens, Nuclear, Cell Line, Cloning, Molecular, DNA, DNA Damage, DNA Helicases, DNA Primers, DNA Repair, DNA-Activated Protein Kinase, DNA-Binding Proteins, Gene Targeting, Humans, Mice, Mice, Knockout, Mutation, Nuclear Proteins, Polymerase Chain Reaction, Recombination, Genetic, Sister Chromatid Exchange, Transcription Factors