原创力文档a multi-step pathway for the establishment of sister chromatid cohesion一个多步骤的途径建立姊妹染色单体凝聚力.pdfVIP
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a multi-step pathway for the establishment of sister chromatid cohesion一个多步骤的途径建立姊妹染色单体凝聚力
A Multi-Step Pathway for the Establishment of
Sister Chromatid Cohesion
1,2,3 ¨ 1,2,3 1,2,4 5 1,2,3*
Mark Milutinovich , Elc¸in Unal , Chris Ward , Robert V. Skibbens , Douglas Koshland
1 Howard Hughes Medical Institute, Carnegie Institution, Baltimore, Maryland, United States of America, 2 Department of Embryology, Carnegie Institution, Baltimore,
Maryland, United States of America, 3 Department of Biology, Johns Hopkins University, Baltimore, Maryland, United States of America, 4 Ingenuity Program, Baltimore
Polytechnic Institute, Baltimore, Maryland, United States of America, 5 Department of Biological Sciences, Lehigh University, Bethlehem, Pennsylvania, United States of
America
The cohesion of sister chromatids is mediated by cohesin, a protein complex containing members of the structural
maintenance of chromosome (Smc) family. How cohesins tether sister chromatids is not yet understood. Here, we
mutate SMC1, the gene encoding a cohesin subunit of budding yeast, by random insertion dominant negative
mutagenesis to generate alleles that are highly informative for cohesin assembly and function. Cohesins mutated in
the Hinge or Loop1 regions of Smc1 bind chromatin by a mechanism similar to wild-type cohesin, but fail to enrich at
cohesin-associated regions (CARs) and pericentric regions. Hence, the Hinge and Loop1 regions of Smc1 are essential
for the specific chromatin binding of cohesin. This specific binding and a subsequent Ctf7/Eco1-dependent step are
both required for the establishment of cohesion. We propose that a cohesin or cohesin oligomer tethers the sister
chromatids through two chromatin-binding events that are regulated spatially by CAR binding and temporally by Ctf7
activat
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