Polymerase theta-mediated end joining of replication-associated DNA breaks in C. elegans.

ABSTRACT: DNA lesions that block replication fork progression are drivers of cancer-associated genome alterations, but the error-prone DNA repair mechanisms acting on collapsed replication are incompletely understood, and their contribution to genome evolution largely unexplored. Here, through whole-genome sequencing of animal populations that were clonally propagated for more than 50 generations, we identify a distinct class of deletions that spontaneously accumulate in C. elegans strains lacking translesion synthesis (TLS) polymerases. Emerging DNA double-strand breaks are repaired via an error-prone mechanism in which the outermost nucleotide of one end serves to prime DNA synthesis on the other end. This pathway critically depends on the A-family polymerase theta, which protects the genome again

SUBMITTER: Roerink SF 

PROVIDER: S-EPMC4032859 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature