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Srs2 overexpression reveals a helicase-independent role at replication forks that requires diverse cell functions.

Abstract：

:Srs2 is a 3'-5' DNA helicase that regulates many aspects of DNA metabolism in Saccharomyces cerevisiae. It is best known for its ability to counteract homologous recombination by dismantling Rad51 filaments, but is also involved in checkpoint activation, adaptation and recovery, and in resolution of late recombination intermediates. To further address its biological roles and uncover new genetic interactions, we examined the consequences of overexpressing SRS2 as well as two helicase-dead mutants, srs2-K41A and srs2-K41R, in the collection of 4827 yeast haploid deletion mutants. We identified 274 genes affecting a large variety of cellular functions that are required for cell growth when SRS2 or its mutants are overexpressed. Further analysis of these interactions reveals that Srs2 acts independently of its helicase function at replication forks likely through its recruitment by the sumoylated PCNA replication clamp. This helicase-independent function is responsible for the negative interactions with DNA metabolism genes and for the toxicity of SRS2 overexpression in many of the diverse cellular pathways revealed in our screens.

journal_name

DNA Repair (Amst)

journal_title

DNA repair

authors

León Ortiz AM,Reid RJ,Dittmar JC,Rothstein R,Nicolas A

doi

10.1016/j.dnarep.2011.02.004

subject

Has Abstract

pub_date

2011-05-05 00:00:00

pages

506-17

issue

5

eissn

1568-7864

issn

1568-7856

pii

S1568-7864(11)00056-5

journal_volume

10

pub_type

杂志文章

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