Wapl controls the dynamic association of cohesin with chromatin

Stephanie Kueng; Björn Hegemann; Beate H Peters; Jesse J Lipp; Alexander Schleiffer; Karl Mechtler; Jan-Michael Peters

doi:10.1016/j.cell.2006.09.040

Wapl controls the dynamic association of cohesin with chromatin

Cell. 2006 Dec 1;127(5):955-67. doi: 10.1016/j.cell.2006.09.040. Epub 2006 Nov 16.

Authors

Stephanie Kueng¹, Björn Hegemann, Beate H Peters, Jesse J Lipp, Alexander Schleiffer, Karl Mechtler, Jan-Michael Peters

Affiliation

¹ Research Institute of Molecular Pathology, Dr. Bohr-Gasse 7, A-1030 Vienna, Austria.

PMID: 17113138
DOI: 10.1016/j.cell.2006.09.040

Abstract

Cohesin establishes sister-chromatid cohesion from S phase until mitosis or meiosis. To allow chromosome segregation, cohesion has to be dissolved. In vertebrate cells, this process is mediated in part by the protease separase, which destroys a small amount of cohesin, but most cohesin is removed from chromosomes without proteolysis. How this is achieved is poorly understood. Here, we show that the interaction between cohesin and chromatin is controlled by Wapl, a protein implicated in heterochromatin formation and tumorigenesis. Wapl is associated with cohesin throughout the cell cycle, and its depletion blocks cohesin dissociation from chromosomes during the early stages of mitosis and prevents the resolution of sister chromatids until anaphase, which occurs after a delay. Wapl depletion also increases the residence time of cohesin on chromatin in interphase. Our data indicate that Wapl is required to unlock cohesin from a particular state in which it is stably bound to chromatin.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Amino Acid Sequence
Carrier Proteins / chemistry
Carrier Proteins / metabolism*
Cell Cycle Proteins / metabolism*
Chromatids / metabolism
Chromatin / metabolism*
Chromosomal Proteins, Non-Histone / metabolism*
Chromosomes, Human / genetics
Cohesins
Conserved Sequence
DNA-Binding Proteins
Evolution, Molecular
Humans
Interphase
Multiprotein Complexes / metabolism
Nuclear Proteins / metabolism*
Oncogene Proteins / chemistry
Oncogene Proteins / metabolism*
Phosphoproteins / metabolism
Phosphorylation
Prophase
Protein Binding
Protein Structure, Secondary
Proto-Oncogene Proteins
Repetitive Sequences, Amino Acid
Saccharomyces cerevisiae
Saccharomyces cerevisiae Proteins / metabolism
Telophase

Substances

Carrier Proteins
Cell Cycle Proteins
Chromatin
Chromosomal Proteins, Non-Histone
DNA-Binding Proteins
MAU2 protein, human
MCD1 protein, S cerevisiae
Multiprotein Complexes
Nuclear Proteins
Oncogene Proteins
Phosphoproteins
Proto-Oncogene Proteins
RAD61 protein, S cerevisiae
SGO1 protein, human
Saccharomyces cerevisiae Proteins
WAPL protein, human