Extensive loss of heterozygosity is suppressed during homologous repair of chromosomal breaks.

摘要: Loss of heterozygosity (LOH) is a common genetic alteration in tumors and often extends several megabases to encompass multiple loci or even whole chromosome arms. Based on marker karyotype analysis tumor samples, significant fraction LOH events appears arise from mitotic recombination between homologous chromosomes, reminiscent during meiosis. As DNA double-strand breaks (DSBs) initiate meiotic recombination, potential mechanism leading mitotically dividing cells DSB repair involving chromosomes. We therefore sought characterize the extent arising DSB-induced chromosomes mammalian cells. To this end, reporter was introduced into mouse embryonic stem cell line that has nonisogenic maternal paternal as case human populations, then one Recombinants alleles were readily obtained at frequency 4.6 x 10(-5); however, substantially lower than by nonhomologous end joining inferred sister chromatids. Strikingly, majority recombinants had restricted site DSB, with minor class having extended markers 6 kb DSB. Furthermore, we found no evidence extending 1 centimorgan more In addition, crossing over, which can lead arm, not observed, implying there are key differences mechanisms. These results indicate extensive normally suppressed allelic