Heterochromatin and cohesion protection at human centromeres: the final say of a long controversy?
| Autor: | Javerzat, Jean-Paul, Javerzat, Jean‐Paul |
|---|---|
| Přispěvatelé: | Institut de biochimie et génétique cellulaires (IBGC), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS) |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Chromosomal Proteins Non-Histone Heterochromatin [SDV]Life Sciences [q-bio] Centromere Cell Cycle Proteins Biology Biochemistry 03 medical and health sciences MESH: Cell Cycle Proteins MESH: Chromosomal Proteins Non-Histone Schizosaccharomyces Genetics Humans Sister chromatids Molecular Biology Mitosis ComputingMilieux_MISCELLANEOUS MESH: Humans Cohesin Scientific Reports Spindle apparatus Chromatin Cell biology MESH: Heterochromatin MESH: Schizosaccharomyces 030104 developmental biology MESH: Centromere Heterochromatin protein 1 |
| Zdroj: | EMBO Reports EMBO Reports, EMBO Press, 2018, 19 (4), ⟨10.15252/embr.201845980⟩ |
| ISSN: | 1469-3178 1469-221X |
| DOI: | 10.15252/embr.201845980 |
| Popis: | Heterochromatin protein‐1 (HP1) is a key component of heterochromatin. Reminiscent of the cohesin complex which mediates sister‐chromatid cohesion, most HP1 proteins in mammalian cells are displaced from chromosome arms during mitotic entry, whereas a pool remains at the heterochromatic centromere region. The function of HP1 at mitotic centromeres remains largely elusive. Here, we show that double knockout (DKO) of HP1α and HP1γ causes defective mitosis progression and weakened centromeric cohesion. While mutating the chromoshadow domain (CSD) prevents HP1α from protecting sister‐chromatid cohesion, centromeric targeting of HP1α CSD alone is sufficient to rescue the cohesion defects in HP1 DKO cells. Interestingly, HP1‐dependent cohesion protection requires Haspin, an antagonist of the cohesin‐releasing factor Wapl. Moreover, HP1α CSD directly binds the N‐terminal region of Haspin and facilitates its centromeric localization. The need for HP1 in cohesion protection can be bypassed by centromeric targeting of Haspin or inhibiting Wapl activity. Taken together, these results reveal a redundant role for HP1α and HP1γ in the protection of centromeric cohesion through promoting Haspin localization at mitotic centromeres in mammalian cells. |
| Databáze: | OpenAIRE |
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