Vertebrate POLQ and POLbeta Cooperate in Base Excision Repair of Oxidative DNA Damage

Overview

Journal Mol Cell

Publisher Cell Press

Specialty Cell Biology

Date 2006 Oct 5

PMID 17018297

Citations 79

Authors

Michio Yoshimura

Masaoki Kohzaki

Jun Nakamura

Kenjiro Asagoshi

Eiichiro Sonoda

Esther Hou

Rajendra Prasad

Samuel H Wilson

Keizo Tano

Akira Yasui

Li Lan

Mineaki Seki

Richard D Wood

Hiroshi Arakawa

Jean-Marie Buerstedde

Helfrid Hochegger

Takashi Okada

Masahiro Hiraoka

Shunichi Takeda

Affiliations

Soon will be listed here.

Abstract

Base excision repair (BER) plays an essential role in protecting cells from mutagenic base damage caused by oxidative stress, hydrolysis, and environmental factors. POLQ is a DNA polymerase, which appears to be involved in translesion DNA synthesis (TLS) past base damage. We disrupted POLQ, and its homologs HEL308 and POLN in chicken DT40 cells, and also created polq/hel308 and polq/poln double mutants. We found that POLQ-deficient mutants exhibit hypersensitivity to oxidative base damage induced by H(2)O(2), but not to UV or cisplatin. Surprisingly, this phenotype was synergistically increased by concomitant deletion of the major BER polymerase, POLbeta. Moreover, extracts from a polq null mutant cell line show reduced BER activity, and POLQ, like POLbeta, accumulated rapidly at sites of base damage. Accordingly, POLQ and POLbeta share an overlapping function in the repair of oxidative base damage. Taken together, these results suggest a role for vertebrate POLQ in BER.

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