Factors Affecting Template Switch Recombination Associated with Restarted DNA Replication

Overview

Journal Elife

Specialty Biology

Date 2019 Jan 23

PMID 30667359

Citations 26

Authors

Manisha Jalan

Judith Oehler

Carl A Morrow

Fekret Osman

Matthew C Whitby

Affiliations

Soon will be listed here.

Abstract

Homologous recombination helps ensure the timely completion of genome duplication by restarting collapsed replication forks. However, this beneficial function is not without risk as replication restarted by homologous recombination is prone to template switching (TS) that can generate deleterious genome rearrangements associated with diseases such as cancer. Previously we established an assay for studying TS in (Nguyen et al., 2015). Here, we show that TS is detected up to 75 kb downstream of a collapsed replication fork and can be triggered by head-on collision between the restarted fork and RNA Polymerase III transcription. The Pif1 DNA helicase, Pfh1, promotes efficient restart and also suppresses TS. A further three conserved helicases (Fbh1, Rqh1 and Srs2) strongly suppress TS, but there is no change in TS frequency in cells lacking Fml1 or Mus81. We discuss how these factors likely influence TS.

Citing Articles

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