Genetic analysis of Saccharomyces cerevisiae H2A serine 129 mutant suggests a functional relationship between H2A and the sister-chromatid cohesion partners Csm3-Tof1 for the repair of topoisomerase I-induced DNA damage.
Collision between a topoisomerase I-DNA intermediate and an advancing replication fork represents a unique form of replicative damage. We have shown previously that yeast H2A serine 129 is involved in the recovery from this type of damage. We now report that efficient repair also requires proteins involved in chromatid cohesion: Csm3; Tof1; Mrc1, and Dcc1. Epistasis analysis defined several pathways involving these proteins. Csm3 and Tof1 function in a same pathway and downstream of H2A. In addition, the pathway involving H2A/Csm3/Tof1 is distinct from the pathways involving the Ctf8/Ctf18/Dcc1 complex, the Rad9 pathway, and another involving Mrc1. Our genetic studies suggest a role for H2A serine 129 in the establishment of specialized cohesion structure necessary for the normal repair of topoisomerase I-induced DNA damage.
Redon
Christophe
C
NIH, NCI, DBS, Laboratory of Molecular Pharmacology, Bethesda, Maryland 20892, USA.
Pilch
Duane R
DR
Bonner
William M
WM
D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002842:Chromatids / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D004261:DNA Replication; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D006657:Histones / Q000235:genetics* / Q000378:metabolism*; D009154:Mutation / Q000235:genetics*; D051721:Rad52 DNA Repair and Recombination Protein / Q000235:genetics / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics* / Q000378:metabolism; D012694:Serine / Q000737:chemistry / Q000235:genetics
C092693:CTF18 protein, S cerevisiae; D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; C429768:Ctf8 protein, S cerevisiae; D004268:DNA-Binding Proteins; C429769:Dcc1 protein, S cerevisiae; D006657:Histones; C441579:MRC1 protein, S cerevisiae; D051721:Rad52 DNA Repair and Recombination Protein; D029701:Saccharomyces cerevisiae Proteins; C119636:TOF1 protein, S cerevisiae; D012694:Serine; D004264:DNA Topoisomerases, Type I