TY - JOUR

T1 - Fission yeast Rad50 stimulates sister chromatid recombination and links cohesion with repair

AU - Hartsuiker, E.

AU - Vaessen, E.

AU - Carr, A.M.

AU - Kohli, J.

PY - 2001/12/3

Y1 - 2001/12/3

N2 - 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.

AB - 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.

KW - Amino Acid Sequence

KW - Animals

KW - Caenorhabditis elegans

KW - Caenorhabditis elegans Proteins

KW - Cell Cycle Proteins

KW - Cell Separation

KW - Chromosomal Proteins, Non-Histone

KW - Chromosome Deletion

KW - Cloning, Molecular

KW - Crosses, Genetic

KW - DNA Damage

KW - DNA Repair

KW - DNA Replication

KW - DNA-Binding Proteins

KW - Dose-Response Relationship, Drug

KW - Dose-Response Relationship, Radiation

KW - Epistasis, Genetic

KW - Flow Cytometry

KW - Fungal Proteins

KW - Gamma Rays

KW - Gene Deletion

KW - Genotype

KW - Humans

KW - Hydroxyurea

KW - Methyl Methanesulfonate

KW - Mice

KW - Models, Genetic

KW - Molecular Sequence Data

KW - Nuclear Proteins

KW - Phosphoproteins

KW - Recombination, Genetic

KW - S Phase

KW - Saccharomyces cerevisiae Proteins

KW - Schizosaccharomyces

KW - Schizosaccharomyces pombe Proteins

KW - Sequence Homology, Amino Acid

KW - Sister Chromatid Exchange

KW - Telomere

KW - Time Factors

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1093/emboj/20.23.6660

DO - 10.1093/emboj/20.23.6660

M3 - Article

C2 - 11726502

VL - 20

SP - 6660

EP - 6671

JO - EMBO Journal

JF - EMBO Journal

SN - 0261-4189

IS - 23

ER -