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The Kinetochore Receptor for the Cohesin Loading Complex

Journal Article · · Cell
 [1];  [2];  [3];  [2]
  1. Harvard Medical School, Boston, MA (United States)
  2. Univ. of Edinburgh (United Kingdom)
  3. Harvard Medical School, Boston, MA (United States); Howard Hughes Medical Inst., Chevy Chase, MD (United States)
The ring-shaped cohesin complex brings together distant DNA domains to maintain, express, and segregate the genome. Establishing specific chromosomal linkages depends on cohesin recruitment to defined loci. One such locus is the budding yeast centromere, which is a paradigm for targeted cohesin loading. The kinetochore, a multiprotein complex that connects centromeres to microtubules, drives the recruitment of high levels of cohesin to link sister chromatids together. We have exploited this system to determine the mechanism of specific cohesin recruitment. We show that phosphorylation of the Ctf19 kinetochore protein by a conserved kinase, DDK, provides a binding site for the Scc2/4 cohesin loading complex, thereby directing cohesin loading to centromeres. A similar mechanism targets cohesin to chromosomes in vertebrates. These findings represent a complete molecular description of targeted cohesin loading, a phenomenon with wide-ranging importance in chromosome segregation and, in multicellular organisms, transcription regulation.
Research Organization:
Argonne National Laboratory (ANL), Argonne, IL (United States)
Sponsoring Organization:
NIH; Wellcome Centre for Cell Biology
OSTI ID:
1430320
Journal Information:
Cell, Journal Name: Cell Journal Issue: 1 Vol. 171; ISSN 0092-8674
Publisher:
ElsevierCopyright Statement
Country of Publication:
United States
Language:
ENGLISH

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Cited By (17)

Kinetochores, cohesin, and DNA breaks: Controlling meiotic recombination within pericentromeres journal February 2019
Paf1 and Ctr9 subcomplex formation is essential for Paf1 complex assembly and functional regulation journal September 2018
Convergent genes shape budding yeast pericentromeres journal April 2020
Rapid high-resolution measurement of DNA replication timing by droplet digital PCR journal July 2018
HiGlass: web-based visual exploration and analysis of genome interaction maps journal August 2018
Evolutionary repair: Changes in multiple functional modules allow meiotic cohesin to support mitosis journal March 2020
Error‐free DNA damage tolerance pathway is facilitated by the Irc5 translocase through cohesin journal August 2018
Budding yeast Rif1 binds to replication origins and protects DNA at blocked replication forks journal July 2018
Budding yeast Rif1 binds to replication origins and protects DNA at blocked replication forks journal June 2019
Overlapping Roles in Chromosome Segregation for Heterochromatin Protein 1 (Swi6) and DDK in Schizosaccharomyces pombe journal April 2019
Topological in vitro loading of the budding yeast cohesin ring onto DNA journal October 2018
The CDK Pef1 and protein phosphatase 4 oppose each other for regulating cohesin binding to fission yeast chromosomes journal January 2020
MCM2–7-dependent cohesin loading during S phase promotes sister-chromatid cohesion journal April 2018
Structural basis for Scc3-dependent cohesin recruitment to chromatin journal August 2018
The COMA complex interacts with Cse4 and positions Sli15/Ipl1 at the budding yeast inner kinetochore journal May 2019
The structure of the Ctf19c/CCAN from budding yeast journal February 2019
The structure of the yeast Ctf3 complex journal June 2019

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