Mechanisms restraining break-induced replication at two-ended DNA double-strand breaks.

摘要: DNA synthesis during homologous recombination is highly mutagenic and prone to template switches. Two-ended double-strand breaks (DSBs) are usually repaired by gene conversion with a short patch of synthesis, thus limiting the mutation load vicinity DSB. Single-ended DSBs break-induced replication (BIR), which involves extensive spanning up hundreds kilobases. It remains unknown how BIR suppressed at two-ended DSBs. Here, we demonstrate that proteins coordinating usage two ends DSB: (i) ssDNA annealing Rad52 Rad59 promote second end capture, (ii) D-loop unwinding helicase Mph1, (iii) Mre11-Rad50-Xrs2 complex promotes synchronous resection Finally, also when Sir2 silences normally heterochromatic repair template. All these particularly important for occurs between repetitive sequences, emphasizing significance mechanisms species carrying many elements such as humans.