Fission yeast Rad50 stimulates sister chromatid recombination and links cohesion with repair.
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.
Hartsuiker
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Genome Damage and Stability Centre, University of Sussex, Falmer, Brighton BN1 9RR, UK.
Vaessen
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Carr
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AM
Kohli
J
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D000595:Amino Acid Sequence; D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D002469:Cell Separation; D002868:Chromosomal Proteins, Non-Histone; D002872:Chromosome Deletion; D003001:Cloning, Molecular; D003433:Crosses, Genetic; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication; D004268:DNA-Binding Proteins; D004305:Dose-Response Relationship, Drug; D004307:Dose-Response Relationship, Radiation; D004843:Epistasis, Genetic; D005434:Flow Cytometry; D005656:Fungal Proteins / Q000235:genetics* / Q000378:metabolism* / Q000502:physiology; D005720:Gamma Rays; D017353:Gene Deletion; D005838:Genotype; D006801:Humans; D006918:Hydroxyurea / Q000494:pharmacology; D008741:Methyl Methanesulfonate / Q000494:pharmacology; D051379:Mice; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011995:Recombination, Genetic; D016196:S Phase; D029701:Saccharomyces cerevisiae Proteins; D012568:Schizosaccharomyces / Q000235:genetics* / Q000378:metabolism; D029702:Schizosaccharomyces pombe Proteins; D017386:Sequence Homology, Amino Acid; D012854:Sister Chromatid Exchange; D016615:Telomere / Q000378:metabolism; D013997:Time Factors
D029742:Caenorhabditis elegans Proteins; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; D005656:Fungal Proteins; C490529:MCD1 protein, S cerevisiae; D009687:Nuclear Proteins; D010750:Phosphoproteins; C429022:RAD21 protein, human; C086930:RAD50 protein, S cerevisiae; C092957:Rad21 protein, S pombe; C465862:Rad21 protein, mouse; D029701:Saccharomyces cerevisiae Proteins; D029702:Schizosaccharomyces pombe Proteins; C490530:scc-1 protein, C elegans; D008741:Methyl Methanesulfonate; D006918:Hydroxyurea