TY - JOUR
T1 - An Eco1-independent sister chromatid cohesion establishment pathway in S. cerevisiae
AU - Borges, Vanessa
AU - Smith, Duncan J.
AU - Whitehouse, Iestyn
AU - Uhlmann, Frank
N1 - Funding Information:
Acknowledgements We are grateful to K. Shirahige for his gift of the ac-Smc3 antibody, J. Campbell for yeast strains and G. Kelly for biostatistics support. We thank the members of our laboratory for advice and comments on the manuscript. This work was funded by Cancer Research UK, the European Research Council (F.U., V. B.) and the National Institute of Health Grant R01 GM102253 to I.W. D.J.S. is a HHMI fellow of the Damon Runyon Cancer Research Foundation (DRG-#2046-10).
PY - 2013/3
Y1 - 2013/3
N2 - Cohesion between sister chromatids, mediated by the chromosomal cohesin complex, is a prerequisite for their alignment on the spindle apparatus and segregation in mitosis. Budding yeast cohesin first associates with chromosomes in G1. Then, during DNA replication in S-phase, the replication fork-associated acetyltransferase Eco1 acetylates the cohesin subunit Smc3 to make cohesin's DNA binding resistant to destabilization by the Wapl protein. Whether stabilization of cohesin molecules that happen to link sister chromatids is sufficient to build sister chromatid cohesion, or whether additional reactions are required to establish these links, is not known. In addition to Eco1, several other factors contribute to cohesion establishment, including Ctf4, Ctf18, Tof1, Csm3, Chl1 and Mrc1, but little is known about their roles. Here, we show that each of these factors facilitates cohesin acetylation. Moreover, the absence of Ctf4 and Chl1, but not of the other factors, causes a synthetic growth defect in cells lacking Eco1. Distinct from acetylation defects, sister chromatid cohesion in ctf4Δ and chl1Δ cells is not improved by removing Wapl. Unlike previously thought, we do not find evidence for a role of Ctf4 and Chl1 in Okazaki fragment processing, or of Okazaki fragment processing in sister chromatid cohesion. Thus, Ctf4 and Chl1 delineate an additional acetylation-independent pathway that might hold important clues as to the mechanism of sister chromatid cohesion establishment.
AB - Cohesion between sister chromatids, mediated by the chromosomal cohesin complex, is a prerequisite for their alignment on the spindle apparatus and segregation in mitosis. Budding yeast cohesin first associates with chromosomes in G1. Then, during DNA replication in S-phase, the replication fork-associated acetyltransferase Eco1 acetylates the cohesin subunit Smc3 to make cohesin's DNA binding resistant to destabilization by the Wapl protein. Whether stabilization of cohesin molecules that happen to link sister chromatids is sufficient to build sister chromatid cohesion, or whether additional reactions are required to establish these links, is not known. In addition to Eco1, several other factors contribute to cohesion establishment, including Ctf4, Ctf18, Tof1, Csm3, Chl1 and Mrc1, but little is known about their roles. Here, we show that each of these factors facilitates cohesin acetylation. Moreover, the absence of Ctf4 and Chl1, but not of the other factors, causes a synthetic growth defect in cells lacking Eco1. Distinct from acetylation defects, sister chromatid cohesion in ctf4Δ and chl1Δ cells is not improved by removing Wapl. Unlike previously thought, we do not find evidence for a role of Ctf4 and Chl1 in Okazaki fragment processing, or of Okazaki fragment processing in sister chromatid cohesion. Thus, Ctf4 and Chl1 delineate an additional acetylation-independent pathway that might hold important clues as to the mechanism of sister chromatid cohesion establishment.
KW - Chl1
KW - Cohesin
KW - Ctf4
KW - Eco1
KW - S. cerevisiae
KW - Sister chromatid cohesion
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U2 - 10.1007/s00412-013-0396-y
DO - 10.1007/s00412-013-0396-y
M3 - Article
C2 - 23334284
AN - SCOPUS:84876458231
SN - 0009-5915
VL - 122
SP - 121
EP - 134
JO - Chromosoma
JF - Chromosoma
IS - 1-2
ER -