biostudies-literatureQian MXNIGMS NIH HHS1012-24https://www.ebi.ac.uk/biostudies/studies/S-EPMC3983474biostudies-literatureUnknown153(5)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 ? subunit ?4 s/PSMA8 and/or the catalytic ? 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.CellAcetylation-mediated proteasomal degradation of core histones during DNA repair and spermatogenesis.PMC3983474R01 GM0519235R01GM51923Cha HMiao STsuruta FQian MXCao CLiu SPang YCheng YWang LChen LBZhai YDu BYChiba TGoldberg ALQiu XBLi GHShen YSong WYu YLiu CHZhang XXLi HKomatsu THaratake KYang DHuang HTLi WLiang YNJi DYZhang ZHZhu QQWang GFfalseAcetylation-mediated proteasomal degradation of core histones during DNA repair and spermatogenesis.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 ? subunit ?4 s/PSMA8 and/or the catalytic ? 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.2013-01-01T00:00:00Z2013 May2020-10-29T14:07:42Z2019-03-27T01:24:48ZS-EPMC39834742370673910.1016/j.cell.2013.04.032