Mechanisms of recombination between diverged sequences in wild-type and BLM-deficient mouse and human cells.
Double-strand breaks (DSBs) are particularly deleterious DNA lesions for which cells have developed multiple mechanisms of repair. One major mechanism of DSB repair in mammalian cells is homologous recombination (HR), whereby a homologous donor sequence is used as a template for repair. For this reason, HR repair of DSBs is also being exploited for gene modification in possible therapeutic approaches. HR is sensitive to sequence divergence, such that the cell has developed ways to suppress recombination between diverged ("homeologous") sequences. In this report, we have examined several aspects of HR between homeologous sequences in mouse and human cells. We found that gene conversion tracts are similar for mouse and human cells and are generally < or =100 bp, even in Msh2(-)(/)(-) cells which fail to suppress homeologous recombination. Gene conversion tracts are mostly unidirectional, with no observed mutations. Additionally, no alterations were observed in the donor sequences. While both mouse and human cells suppress homeologous recombination, the suppression is substantially less in the transformed human cells, despite similarities in the gene conversion tracts. BLM-deficient mouse and human cells suppress homeologous recombination to a similar extent as wild-type cells, unlike Sgs1-deficient Saccharomyces cerevisiae.
Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
Jeannine R
JR
Larocque
Maria
M
Jasin
D000818:Animals; D020137:Base Pair Mismatch; D001483:Base Sequence; D002460:Cell Line; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D006801:Humans; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D051718:MutS Homolog 2 Protein / Q000235:genetics / Q000378:metabolism; D053484:RecQ Helicases / Q000235:genetics* / Q000378:metabolism; D011995:Recombination, Genetic
C097151:Bloom syndrome protein; D051718:MutS Homolog 2 Protein; D053484:RecQ Helicases