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The replicative helicase MCM recruits cohesin acetyltransferase ESCO2 to mediate centromeric sister chromatid cohesion
Author(s) -
Ivanov Miroslav P,
Ladurner Rene,
Poser Ina,
Beveridge Rebecca,
Rampler Evelyn,
Hudecz Otto,
Novatchkova Maria,
Hériché JeanKarim,
Wutz Gordana,
Lelij Petra,
Kreidl Emanuel,
Hutchins James RA,
AxelssonEkker Heinz,
Ellenberg Jan,
Hyman Anthony A,
Mechtler Karl,
Peters JanMichael
Publication year - 2018
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.15252/embj.201797150
Subject(s) - cohesin , establishment of sister chromatid cohesion , biology , chromosome segregation , helicase , kinetochore , chromatin , separase , genetics , dna replication , microbiology and biotechnology , chromosome , dna , rna , gene
Chromosome segregation depends on sister chromatid cohesion which is established by cohesin during DNA replication. Cohesive cohesin complexes become acetylated to prevent their precocious release by WAPL before cells have reached mitosis. To obtain insight into how DNA replication, cohesion establishment and cohesin acetylation are coordinated, we analysed the interaction partners of 55 human proteins implicated in these processes by mass spectrometry. This proteomic screen revealed that on chromatin the cohesin acetyltransferase ESCO 2 associates with the MCM 2‐7 subcomplex of the replicative Cdc45‐ MCM ‐ GINS helicase. The analysis of ESCO 2 mutants defective in MCM binding indicates that these interactions are required for proper recruitment of ESCO 2 to chromatin, cohesin acetylation during DNA replication, and centromeric cohesion. We propose that MCM binding enables ESCO 2 to travel with replisomes to acetylate cohesive cohesin complexes in the vicinity of replication forks so that these complexes can be protected from precocious release by WAPL . Our results also indicate that ESCO 1 and ESCO 2 have distinct functions in maintaining cohesion between chromosome arms and centromeres, respectively.