Format

Send to

Choose Destination
J Cell Sci. 2015 May 1;128(9):1732-45. doi: 10.1242/jcs.162305. Epub 2015 Mar 20.

CRL4(RBBP7) is required for efficient CENP-A deposition at centromeres.

Author information

1
Department of Biology, Institute of Biochemistry, Swiss Federal Institute of Technology, 8093 Zurich, Switzerland.
2
Department of Biology, Institute of Biochemistry, Swiss Federal Institute of Technology, 8093 Zurich, Switzerland Department of Physiology and Metabolism, Faculty of Medicine, University of Geneva, 1211 Geneva, Switzerland.
3
Department of Biology, Institute of Biochemistry, Swiss Federal Institute of Technology, 8093 Zurich, Switzerland matthias.peter@bc.biol.ethz.ch.

Abstract

The mitotic spindle drives chromosome movement during mitosis and attaches to chromosomes at dedicated genomic loci named centromeres. Centromeres are epigenetically specified by their histone composition, namely the presence of the histone H3 variant CENP-A, which is regulated during the cell cycle by its dynamic expression and localization. Here, we combined biochemical methods and quantitative imaging approaches to investigate a new function of CUL4-RING E3 ubiquitin ligases (CRL4) in regulating CENP-A dynamics. We found that the core components CUL4 and DDB1 are required for centromeric loading of CENP-A, but do not influence CENP-A maintenance or pre-nucleosomal CENP-A levels. Interestingly, we identified RBBP7 as a substrate-specific CRL4 adaptor required for this process, in addition to its role in binding and stabilizing soluble CENP-A. Our data thus suggest that the CRL4 complex containing RBBP7 (CRL4(RBBP7)) might regulate mitosis by promoting ubiquitin-dependent loading of newly synthesized CENP-A during the G1 phase of the cell cycle.

KEYWORDS:

CENP‐A; Centromere; Cullin; RBBP7

PMID:
25795299
DOI:
10.1242/jcs.162305
[Indexed for MEDLINE]
Free full text

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center