Acetylation-mediated proteasomal degradation of core histones during DNA repair and spermatogenesis.
Cell
; 153(5): 1012-24, 2013 May 23.
Article
in En
| MEDLINE
| ID: mdl-23706739
ABSTRACT
Histone acetylation plays critical roles in chromatin remodeling, DNA repair, and epigenetic regulation of gene expression, but the underlying mechanisms are unclear. Proteasomes usually catalyze ATP- and polyubiquitin-dependent proteolysis. Here, we show that the proteasomes containing the activator PA200 catalyze the polyubiquitin-independent degradation of histones. Most proteasomes in mammalian testes ("spermatoproteasomes") contain a spermatid/sperm-specific α subunit α4 s/PSMA8 and/or the catalytic ß subunits of immunoproteasomes in addition to PA200. Deletion of PA200 in mice abolishes acetylation-dependent degradation of somatic core histones during DNA double-strand breaks and delays core histone disappearance in elongated spermatids. Purified PA200 greatly promotes ATP-independent proteasomal degradation of the acetylated core histones, but not polyubiquitinated proteins. Furthermore, acetylation on histones is required for their binding to the bromodomain-like regions in PA200 and its yeast ortholog, Blm10. Thus, PA200/Blm10 specifically targets the core histones for acetylation-mediated degradation by proteasomes, providing mechanisms by which acetylation regulates histone degradation, DNA repair, and spermatogenesis.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Spermatogenesis
/
Testis
/
Nuclear Proteins
/
Histones
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Proteasome Endopeptidase Complex
/
DNA Repair
Limits:
Animals
/
Humans
/
Male
Language:
En
Journal:
Cell
Year:
2013
Type:
Article
Affiliation country:
China