SMC1 coordinates DNA double-strand break repair pathways.
The SMC1/SMC3 heterodimer acts in sister chromatid cohesion, and recent data indicate a function in DNA double-strand break repair (DSBR). Since this role of SMC proteins has remained largely elusive, we explored interactions between SMC1 and the homologous recombination (HR) or non-homologous end-joining (NHEJ) pathways for DSBR in Saccharomyces cerevisiae. Analysis of conditional single- and double mutants of smc1-2 with rad52Delta, rad54Delta, rad50Delta or dnl4Delta illustrates a significant contribution of SMC1 to the overall capacity of cells to repair DSBs. smc1 but not smc2 mutants show increased hypersensitivity of HR mutants to ionizing irradiation and to the DNA crosslinking agent cis-platin. Haploid, but not diploid smc1-2 mutants were severely affected in repairing multiple genomic DNA breaks, suggesting a selective role of SMC1 in sister chromatid recombination. smc1-2 mutants were also 15-fold less efficient and highly error-prone in plasmid end-joining through the NHEJ pathway. Strikingly, inactivation of RAD52 or RAD54 fully rescued efficiency and accuracy of NHEJ in the smc1 background. Therefore, we propose coordination of HR and NHEJ processes by Smc1p through interaction with the RAD52 pathway.
Schär
Primo
P
Institute of Biochemistry and Genetics, DKBW, University of Basel, CH-4058 Basel, Switzerland. primo.schaer@unibas.ch
Fäsi
Margaret
M
Jessberger
Rolf
R
D001483:Base Sequence; D018797:Cell Cycle Proteins / Q000235:genetics / Q000502:physiology*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000502:physiology*; D002945:Cisplatin / Q000633:toxicity; D003432:Cross-Linking Reagents / Q000633:toxicity; D004249:DNA Damage; D004260:DNA Repair; D008969:Molecular Sequence Data; D009154:Mutation; D011839:Radiation, Ionizing; D011995:Recombination, Genetic; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D016615:Telomere / Q000737:chemistry; D000098550:Structural Maintenance of Chromosome Protein 1
D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; D003432:Cross-Linking Reagents; D029701:Saccharomyces cerevisiae Proteins; D000098550:Structural Maintenance of Chromosome Protein 1; D002945:Cisplatin