Polμ tumor variants decrease the efficiency and accuracy of NHEJ.

ABSTRACT: The non homologous end-joining (NHEJ) pathway of double-strand break (DSB) repair often requires DNA synthesis to fill the gaps generated upon alignment of the broken ends, a complex task performed in human cells by two specialized DNA polymerases, Polλ and Polμ. It is now well established that Polμ is the one adapted to repair DSBs with non-complementary ends, the most challenging scenario, although the structural basis and physiological implications of this adaptation are not fully understood. Here, we demonstrate that two human Polμ point mutations, G174S and R175H, previously identified in two different tumor samples and affecting two adjacent residues, limit the efficiency of accurate NHEJ by Polμ in vitro and in vivo. Moreover, we show that this limitation is the consequence of a dec

SUBMITTER: Sastre-Moreno G 

PROVIDER: S-EPMC5622330 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature