Characterization of a natural mutator variant of human DNA polymerase lambda which promotes chromosomal instability by compromising NHEJ.

ABSTRACT:

Background

DNA polymerase lambda (Pollambda) is a DNA repair polymerase, which likely plays a role in base excision repair (BER) and in non-homologous end joining (NHEJ) of DNA double-strand breaks (DSB).

Principal findings

Here, we described a novel natural allelic variant of human Pollambda (hPollambda) characterized by a single nucleotide polymorphism (SNP), C/T variation in the first base of codon 438, resulting in the amino acid change Arg to Trp. In vitro enzyme activity assays of the purified W438 Pollambda variant revealed that it retained both DNA polymerization and deoxyribose phosphate (dRP) lyase activities, but had reduced base substitution fidelity. Ectopic expression of the W438 hPollambda variant in mammalian cells increases mutation frequency, affects the DS

SUBMITTER: Terrados G 

PROVIDER: S-EPMC2751832 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature