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PMID: 11726502 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Fission yeast Rad50 stimulates sister chromatid recombination and links cohesion with repair.

The EMBO journal ·Vol. 20 ·No. 23 ·2001-12-03 ·Pages 6660-71

Hartsuiker E, Vaessen E, Carr AM, Kohli J

Abstract

To study the role of Rad50 in the DNA damage response, we cloned and deleted the Schizosaccharomyces pombe RAD50 homologue. The deletion is sensitive to a range of DNA-damaging agents and shows dynamic epistatic interactions with other recombination-repair genes. We show that Rad50 is necessary for recombinational repair of the DNA lesion at the mating-type locus and that rad50Delta shows slow DNA replication. We also find that Rad50 is not required for slowing down S phase in response to hydroxy urea or methyl methanesulfonate (MMS) treatment. Interestingly, in rad50Delta cells, the recombination frequency between two homologous chromosomes is increased at the expense of sister chromatid recombination. We propose that Rad50, an SMC-like protein, promotes the use of the sister chromatid as the template for homologous recombinational repair. In support of this, we found that Rad50 functions in the same pathway for the repair of MMS-induced damage as Rad21, the homologue of the Saccharomyces cerevisiae Scc1 cohesin protein. We speculate that Rad50 interacts with the cohesin complex during S phase to assist repair and possibly re-initiation of replication after replication fork collapse.

MeSH Terms
Amino Acid Sequence Animals Caenorhabditis elegans Caenorhabditis elegans Proteins Cell Cycle Proteins Cell Separation Chromosomal Proteins, Non-Histone Chromosome Deletion Cloning, Molecular Crosses, Genetic DNA Damage DNA Repair DNA Replication DNA-Binding Proteins Dose-Response Relationship, Drug Dose-Response Relationship, Radiation Epistasis, Genetic Flow Cytometry Fungal Proteins/genetics,metabolism,physiology Gamma Rays Gene Deletion Genotype Humans Hydroxyurea/pharmacology Methyl Methanesulfonate/pharmacology Mice Models, Genetic Molecular Sequence Data Nuclear Proteins/genetics,metabolism Phosphoproteins/genetics,metabolism Recombination, Genetic S Phase Saccharomyces cerevisiae Proteins Schizosaccharomyces/genetics,metabolism Schizosaccharomyces pombe Proteins Sequence Homology, Amino Acid Sister Chromatid Exchange Telomere/metabolism Time Factors
Chemicals
Caenorhabditis elegans Proteins Cell Cycle Proteins Chromosomal Proteins, Non-Histone DNA-Binding Proteins Fungal Proteins MCD1 protein, S cerevisiae Nuclear Proteins Phosphoproteins RAD21 protein, human RAD50 protein, S cerevisiae Rad21 protein, S pombe Rad21 protein, mouse Saccharomyces cerevisiae Proteins Schizosaccharomyces pombe Proteins scc-1 protein, C elegans Methyl Methanesulfonate Hydroxyurea
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Hartsuiker E
Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton BN1 9RR, UK.
Vaessen E
Carr A M
Kohli J
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
DOI
10.1093/emboj/20.23.6660
Published
2001-12-03
Pages
6660-71
Language
English
Region
England
NLM ID
8208664
PMCID
PMC125746
Subset
IM
External Links
PubMed source DOI: 10.1093/emboj/20.23.6660 PMC Full Text View journal details
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