Work

Increased Mutagenesis and Unique Mutation Signature Associated with Mitotic Gene Conversion

Year: 2010

Type: article

Abstract: To examine the fidelity of DNA synthesis during double-strand break (DSB) repair in Saccharomyces cerevisiae we studied gene conversion in which both strands of DNA are newly synthesized. The mutation rate increases up to 1400 times over spontaneous events, with a significantly different mutation signature. Especially prominent are microhomology-mediated template switches. Recombination-induced mutations are largely independent of mismatch repair, by DNA polymerases Polzeta, Poleta, and Pol32, but result from errors made by Poldelta and Polepsilon. These observations suggest that increased DSB frequencies in oncogene-activated mammalian cells may also increase the probability of acquiring mutations required for transition to a cancerous state.

Source: Science

DOI: 10.1126/science.1191125

Authors: Wade M. Hicks, Minlee Kim, James E. Haber

Institution: Brandeis University

Language: English

Topic: DNA Repair Mechanisms

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

Open Access status: green

Funder: National Institute of General Medical Sciences

Awards: G253774738, Genetic and Biochemical Mechanisms of Regulation, RECOMBINATION MECHANISMS IN YEAST CELL DIFFERENTIATION, Recombination Mechanisms in Yeast Cell Differentiation