The ELG1 clamp loader plays a role in sister chromatid cohesion.
Mutations in the ELG1 gene of yeast lead to genomic instability, manifested in high levels of genetic recombination, chromosome loss, and gross chromosomal rearrangements. Elg1 shows similarity to the large subunit of the Replication Factor C clamp loader, and forms a RFC-like (RLC) complex in conjunction with the 4 small RFC subunits. Two additional RLCs exist in yeast: in one of them the large subunit is Ctf18, and in the other, Rad24. Ctf18 has been characterized as the RLC that functions in sister chromatid cohesion. Here we present evidence that the Elg1 RLC (but not Rad24) also plays an important role in this process. A genetic screen identified the cohesin subunit Mcd1/Scc1 and its loader Scc2 as suppressors of the synthetic lethality between elg1 and ctf4. We describe genetic interactions between ELG1 and genes encoding cohesin subunits and their accessory proteins. We also show that defects in Elg1 lead to higher precocious sister chromatid separation, and that Ctf18 and Elg1 affect cohesion via a joint pathway. Finally, we localize both Ctf18 and Elg1 to chromatin and show that Elg1 plays a role in the recruitment of Ctf18. Our results suggest that Elg1, Ctf4, and Ctf18 may coordinate the relative movement of the replication fork with respect to the cohesin ring.
Department of Molecular Microbiology and Biotechnology, Tel Aviv University, Ramat Aviv, Israel.
Oren
O
Parnas
Adi
A
Zipin-Roitman
Yuval
Y
Mazor
Batia
B
Liefshitz
Shay
S
Ben-Aroya
Martin
M
Kupiec
D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D018797:Cell Cycle Proteins / Q000235:genetics / Q000378:metabolism; D002842:Chromatids / Q000502:physiology*; D002843:Chromatin / Q000378:metabolism; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism; D020090:Chromosome Segregation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D009154:Mutation; D010957:Plasmids / Q000235:genetics; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000254:growth & development / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012854:Sister Chromatid Exchange
C092693:CTF18 protein, S cerevisiae; C078338:CTF4 protein, S cerevisiae; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D004268:DNA-Binding Proteins; C477609:Elg1 protein, S cerevisiae; C490529:MCD1 protein, S cerevisiae; C410592:SCC2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins