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PMID: 19158389 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

The Saccharomyces cerevisiae Esc2 and Smc5-6 proteins promote sister chromatid junction-mediated intra-S repair.

Molecular biology of the cell ·Vol. 20 ·No. 6 ·2009-03-00 ·Pages 1671-82

Sollier J, Driscoll R, Castellucci F, Foiani M, Jackson SP, Branzei D

Abstract

Recombination is important for DNA repair, but it can also contribute to genome rearrangements. RecQ helicases, including yeast Sgs1 and human BLM, safeguard genome integrity through their functions in DNA recombination. Sgs1 prevents the accumulation of Rad51-dependent sister chromatid junctions at damaged replication forks, and its functionality seems to be regulated by Ubc9- and Mms21-dependent sumoylation. We show that mutations in Smc5-6 and Esc2 also lead to an accumulation of recombinogenic structures at damaged replication forks. Because Smc5-6 is sumoylated in an Mms21-dependent manner, this finding suggests that Smc5-6 may be a crucial target of Mms21 implicated in this process. Our data reveal that Smc5-6 and Esc2 are required to tolerate DNA damage and that their functionality is critical in genotoxic conditions in the absence of Sgs1. As reported previously for Sgs1 and Smc5-6, we find that Esc2 physically interacts with Ubc9 and SUMO. This interaction is correlated with the ability of Esc2 to promote DNA damage tolerance. Collectively, these data suggest that Esc2 and Smc5-6 act in concert with Sgs1 to prevent the accumulation of recombinogenic structures at damaged replication forks, likely by integrating sumoylation activities to regulate the repair pathways in response to damaged DNA.

MeSH Terms
Cell Cycle Proteins/genetics,metabolism Chromatids/genetics DNA Damage DNA Repair DNA Replication/genetics Mutation/genetics Nuclear Proteins/genetics,metabolism Protein Binding RecQ Helicases/genetics,metabolism S Phase SUMO-1 Protein/metabolism Saccharomyces cerevisiae/cytology,genetics,metabolism Saccharomyces cerevisiae Proteins/genetics,metabolism Ubiquitin-Conjugating Enzymes/metabolism
Chemicals
Cell Cycle Proteins Esc2 protein, S cerevisiae Nuclear Proteins SMC5 protein, S cerevisiae SMC6 protein, S cerevisiae SUMO-1 Protein Saccharomyces cerevisiae Proteins TOP3 protein, S cerevisiae Ubiquitin-Conjugating Enzymes SGS1 protein, S cerevisiae RecQ Helicases
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Sollier Julie
IFOM, The FIRC Institute for Molecular Oncology Foundation, IFOM-IEO Campus, 20139 Milan, Italy.
Driscoll Robert
Castellucci Federica
Foiani Marco
Jackson Stephen P
Branzei Dana
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Article Info
Journal
Molecular biology of the cell
Abbr.
Mol Biol Cell
ISSN
1939-4586
DOI
10.1091/mbc.e08-08-0875
Published
2009-03-00
Epub
2009-00-21
Pages
1671-82
Language
English
Region
United States
NLM ID
9201390
PMCID
PMC2655255
Subset
IM
Grants
Cancer Research UK · A5290 · United Kingdom
Biotechnology and Biological Sciences Research Council · United Kingdom
External Links
PubMed source DOI: 10.1091/mbc.e08-08-0875 PMC Full Text View journal details
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