Regulation of centromere function by R37 methylation and K49 acetylation of CENP-A/ Cse4 in Saccharomyces cerevisiae


Centromeres of eukaryotic chromosomes mark the site for kinetochore formation and microtubule attachment and are essential for accurate chromosome segregation. Centromere identity is defined by the presence of the histone H3 variant CENP-A (Cse4 in Saccharomyces cerevisiae). In this project, we will elucidate the function and interplay of two posttranslational modifications on Cse4 from the yeast S. cerevisiae that we have identified. We have previously reported arginine methylation of Cse4, and we have furthermore identified a novel acetylation site modification. This proposal will aim at identifying the molecular basis for how these modifications mechanistically regulate kinetochore assembly, thus generating molecular knowledge of the regulation of kinetochore assembly and chromosome segregation by posttranslational modification of CENP-A/ Cse4. It thus opens up a new avenue of research into the molecular “interpretation” of PTMs on the centromeric histone variant CENP-A.


Principal Investigators
Ehrenhofer-Murray, Ann Prof. Dr. (Details) (Molecular Cell Biology)

Duration of Project
Start date: 07/2014
End date: 01/2020

Publications
Anedchenko EA*, Samel-Pommerencke A*, Tran Nguyen TM, Shahnejat-Bushehri S, Pöpsel J, Lauster D, Herrmann A, Rappsilber J, Cuomo A, Bonaldi T, Ehrenhofer-Murray, AE (2019) The kinetochore module Okp1CENP-Q/Ame1CENP-U is a reader for N-terminal modifications on the centromeric histone Cse4CENP-A. Embo Journal, DOI: 10.15252/embj.201898991

Shahnejat-Bushehri and Ehrenhofer-Murray, AE (2020) The ATAD2/ ANCCA homolog Yta7 cooperates with Scm3/HJURP to deposit Cse4/CENP A at the centromere in yeast. Proc Natl Acad Sci (in press)

Yan K, Yang J, Zhang Z, McLaughlin SH, Chang L, Fasci D, Ehrenhofer-Murray AE, Heck AJR, Barford D. (2019) Structure of the inner kinetochore CCAN complex assembled onto a centromeric nucleosome. Nature 574(7777):278-282.

Samel A, Nguyen TKL, Ehrenhofer-Murray AE.(2017) Defects in methylation of arginine 37 on CENP-A/Cse4 are compensated by the ubiquitin ligase complex Ubr2/Mub1. FEMS Yeast Res. 2017 Jan 1;17(1).

Hoffmann G, Samel-Pommerencke A, Weber J, Cuomo A, Bonaldi T, Ehrenhofer-Murray AE. (2018) A role for CENP-A/Cse4 phosphorylation on serine 33 in deposition at the centromere. FEMS Yeast Res. 2018 Feb 1;18(1).

Last updated on 2020-12-11 at 12:22