The Shu Complex Promotes Error-free Tolerance of Alkylation-induced Base Excision Repair Products

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2016 Jun 15

PMID 27298254

Citations 18

Authors

Stephen K Godin

Zhuying Zhang

Benjamin W Herken

James W Westmoreland

Alison G Lee

Michael J Mihalevic

Zhongxun Yu

Robert W Sobol

Michael A Resnick

Kara A Bernstein

Affiliations

Soon will be listed here.

Abstract

Here, we investigate the role of the budding yeast Shu complex in promoting homologous recombination (HR) upon replication fork damage. We recently found that the Shu complex stimulates Rad51 filament formation during HR through its physical interactions with Rad55-Rad57. Unlike other HR factors, Shu complex mutants are primarily sensitive to replicative stress caused by MMS and not to more direct DNA breaks. Here, we uncover a novel role for the Shu complex in the repair of specific MMS-induced DNA lesions and elucidate the interplay between HR and translesion DNA synthesis. We find that the Shu complex promotes high-fidelity bypass of MMS-induced alkylation damage, such as N3-methyladenine, as well as bypassing the abasic sites generated after Mag1 removes N3-methyladenine lesions. Furthermore, we find that the Shu complex responds to ssDNA breaks generated in cells lacking the abasic site endonucleases. At each lesion, the Shu complex promotes Rad51-dependent HR as the primary repair/tolerance mechanism over error-prone translesion DNA polymerases. Together, our work demonstrates that the Shu complex's promotion of Rad51 pre-synaptic filaments is critical for high-fidelity bypass of multiple replication-blocking lesion.

Citing Articles

The Shu complex interacts with the replicative helicase to prevent mutations and aberrant recombination.

Fagunloye A, De Magis A, Little J, Contreras I, Dorwart T, Bonilla B EMBO J. 2025; 44(5):1512-1539.

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The human Shu complex promotes RAD51 activity by modulating RPA dynamics on ssDNA.

Hengel S, Oppenheimer K, Smith C, Schaich M, Rein H, Martino J Nat Commun. 2024; 15(1):7197.

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Hrq1/RECQL4 regulation is critical for preventing aberrant recombination during DNA intrastrand crosslink repair and is upregulated in breast cancer.

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