Analysis of the regulatory network of cohesin acetylation

2015 Fiscal Year Final Research Report

• Project/Area Number: 25290065
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: Genome biology
• Research Institution: The University of Tokyo
• Principal Investigator: Bando Masashige 東京大学, 分子細胞生物学研究所, 助教 (90360627)
• Co-Investigator(Kenkyū-buntansha): NAKATO Ryuichiro 東京大学, 分子細胞生物学研究所, 助教 (60583044)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: コヒーシン / アセチル化 / Esco / 姉妹染色分体間接着 / DNA複製 / MCMヘリカーゼ

Outline of Final Research Achievements

There are two cohesin acetyl transferase, Esco1 and Esco2, in human. Both of them are essential for establishment of sister chromatids cohesion. We found that Esco1 directly binds to cohesin subunit Pds5 and co-localizes with cohesin. The domain for binding with Pds5 is responsible for cohesin acetylation and cohesion establishment. Esco1 phosphorylated in mitosis prevents its binding with Pds5. Therefore phosphorylation may have important role in controlling Esco1 localization. Esco2 associates with MCM helicases during G1 to S-phase. The N-terminal domain of Esco2 conserved among vertebrates is required for direct interation with MCM. It has been known that Esco2 is down-regulated from late G2 to M phase. Interestingly Esco2 mutant that is unable to bind to Mcm is destabilized. This destabilization of Esco2 is caused by proteaosome pathway mediated by Cul4 ligase. Thus, Esco1 and Esco2 function in different pathway from each other to promote cell cycle progression.

Free Research Field

ゲノム構造