Heterochromatin and cohesion protection at human centromeres: the final say of a long controversy?

EMBO Rep

Institut de Biochimie et Génétique Cellulaires, UMR 5095, CNRS, Université de Bordeaux, Bordeaux Cedex, France.

Published: April 2018

Mammalian centromeres are embedded within heterochromatin, a specialized chromatin assembled onto repetitive DNA that forms the primary constriction of chromosomes. In early mitosis, the bulk of cohesin dissociates from chromosomes, but a small fraction is spared at the centromere providing the ultimate linker between sister chromatid pairs, essential for their proper attachment to the mitotic spindle. Whether heterochromatin plays a role in the protection of centromere cohesion has long been controversial. In this issue of , Yi show that heterochromatin protein 1 (HP1) isoforms α and γ act redundantly to protect mitotic centromere cohesion through the recruitment of the cohesion protector Haspin 1.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5891423PMC
http://dx.doi.org/10.15252/embr.201845980DOI Listing

Publication Analysis

Top Keywords

centromere cohesion
8
heterochromatin
4
heterochromatin cohesion
4
cohesion protection
4
protection human
4
human centromeres
4
centromeres final
4
final long
4
long controversy?
4
controversy? mammalian
4

Similar Publications

HP1 Promotes the Centromeric Localization of ATRX and Protects Cohesion by Interfering Wapl Activity in Mitosis.

Front Biosci (Landmark Ed)

January 2025

The Key Laboratory of Model Animals and Stem Cell Biology in Hunan Province, Hunan Normal University Health Science Center, 410013 Changsha, Hunan, China.

Background: α thalassemia/mental retardation syndrome X-linked (ATRX) serves as a part of the sucrose nonfermenting 2 (SNF2) chromatin-remodeling complex. In interphase, ATRX localizes to pericentromeric heterochromatin, contributing to DNA double-strand break repair, DNA replication, and telomere maintenance. During mitosis, most ATRX proteins are removed from chromosomal arms, leaving a pool near the centromere region in mammalian cells, which is critical for accurate chromosome congression and sister chromatid cohesion protection.

View Article and Find Full Text PDF

Aneuploidy in eggs is a leading cause of miscarriages or viable developmental syndromes. Aneuploidy rates differ between individual chromosomes. For instance, chromosome 21 frequently missegregates, resulting in Down Syndrome.

View Article and Find Full Text PDF

Stromal antigen 1 and 2 (STAG1 and STAG2) are two mutually exclusive components of the cohesin complex that is crucial for centromeric and telomeric cohesion. Beyond its structural role, STAG2 also plays a pivotal role in homologous recombination (HR) repair and has emerged as a promising therapeutic target in cancer treatment. Here, we employed a fluorescence polarization (FP)-based high-throughput screening and identified KPT-6566 as a dual inhibitor of STAG1 and STAG2.

View Article and Find Full Text PDF

Microtubule poleward flux as a target for modifying chromosome segregation errors.

Proc Natl Acad Sci U S A

November 2024

Laboratory of Cell Biophysics, Division of Molecular Biology, Ruđer Bošković Institute, Zagreb 10000, Croatia.

Cancer cells often display errors in chromosome segregation, some of which result from improper chromosome alignment at the spindle midplane. Chromosome alignment is facilitated by different rates of microtubule poleward flux between sister kinetochore fibers. However, the role of the poleward flux in supporting mitotic fidelity remains unknown.

View Article and Find Full Text PDF

Retrotransposons have invaded eukaryotic centromeres in cycles of repeat expansion and purging, but the function of centromeric retrotransposons has remained unclear. In Arabidopsis, centromeric ATHILA retrotransposons give rise to epigenetically activated short interfering RNAs in mutants in DECREASE IN DNA METHYLATION1 (DDM1). Here we show that mutants that lose both DDM1 and RNA-dependent RNA polymerase have pleiotropic developmental defects and mis-segregate chromosome 5 during mitosis.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!