Translesion Polymerases Drive Microhomology-Mediated Break-Induced Replication Leading to Complex Chromosomal Rearrangements.

ABSTRACT: Complex genomic rearrangements (CGRs) are a hallmark of many human diseases. Recently, CGRs were suggested to result from microhomology-mediated break-induced replication (MMBIR), a replicative mechanism involving template switching at positions of microhomology. Currently, the cause of MMBIR and the proteins mediating this process remain unknown. Here, we demonstrate in yeast that a collapse of homology-driven break-induced replication (BIR) caused by defective repair DNA synthesis in the absence of Pif1 helicase leads to template switches involving 0-6 nt of homology, followed by resolution of recombination intermediates into chromosomal rearrangements. Importantly, we show that these microhomology-mediated template switches, indicative of MMBIR, are driven by translesion synthesis (TLS)

SUBMITTER: Sakofsky CJ 

PROVIDER: S-EPMC4688117 | biostudies-literature | 2015 Dec

REPOSITORIES: biostudies-literature