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Originally published as Genetics Published Articles Ahead of Print on October 11, 2005.
Genetics, Vol. 172, 67-76, January 2006, Copyright © 2006
doi:10.1534/genetics.105.046128
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
Christophe Redon1, Duane R. Pilch and William M. Bonner2
NIH, NCI, DBS, Laboratory of Molecular Pharmacology, Bethesda, Maryland 20892
2 Corresponding author: NIH/NCI/DBS Laboratory of Molecular Pharmacology, Bldg. 37, Room 5050A, 9000 Rockville Pike, Bethesda, MD 20892.
E-mail: wmbonner{at}helix.nih.gov
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.
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