title: Acetylation-mediated proteasomal degradation of core histones during DNA repair and spermatogenesis.
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 β 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.
authors.affiliation: Key Laboratory of Cell Proliferation and Regulation Biology, Ministry of Education, and College of Life Sciences, Beijing Normal University, 19 Xinjiekouwai Avenue, Beijing 100875, China.
authors.forename: Min-Xian
authors.initials: MX
authors.lastname: Qian
authors.forename: Ye
authors.initials: Y
authors.lastname: Pang
authors.forename: Cui Hua
authors.initials: CH
authors.lastname: Liu
authors.forename: Kousuke
authors.initials: K
authors.lastname: Haratake
authors.forename: Bo-Yu
authors.initials: BY
authors.lastname: Du
authors.forename: Dan-Yang
authors.initials: DY
authors.lastname: Ji
authors.forename: Guang-Fei
authors.initials: GF
authors.lastname: Wang
authors.forename: Qian-Qian
authors.initials: QQ
authors.lastname: Zhu
authors.forename: Wei
authors.initials: W
authors.lastname: Song
authors.forename: Yadong
authors.initials: Y
authors.lastname: Yu
authors.forename: Xiao-Xu
authors.initials: XX
authors.lastname: Zhang
authors.forename: Hai-Tao
authors.initials: HT
authors.lastname: Huang
authors.forename: Shiying
authors.initials: S
authors.lastname: Miao
authors.forename: Lian-Bin
authors.initials: LB
authors.lastname: Chen
authors.forename: Zi-Hui
authors.initials: ZH
authors.lastname: Zhang
authors.forename: Ya-Nan
authors.initials: YN
authors.lastname: Liang
authors.forename: Shan
authors.initials: S
authors.lastname: Liu
authors.forename: Hwangho
authors.initials: H
authors.lastname: Cha
authors.forename: Dong
authors.initials: D
authors.lastname: Yang
authors.forename: Yonggong
authors.initials: Y
authors.lastname: Zhai
authors.forename: Takuo
authors.initials: T
authors.lastname: Komatsu
authors.forename: Fuminori
authors.initials: F
authors.lastname: Tsuruta
authors.forename: Haitao
authors.initials: H
authors.lastname: Li
authors.forename: Cheng
authors.initials: C
authors.lastname: Cao
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Guo-Hong
authors.initials: GH
authors.lastname: Li
authors.forename: Yifan
authors.initials: Y
authors.lastname: Cheng
authors.forename: Tomoki
authors.initials: T
authors.lastname: Chiba
authors.forename: Linfang
authors.initials: L
authors.lastname: Wang
authors.forename: Alfred L
authors.initials: AL
authors.lastname: Goldberg
authors.forename: Yan
authors.initials: Y
authors.lastname: Shen
authors.forename: Xiao-Bo
authors.initials: XB
authors.lastname: Qiu
mesh_terms: D000107:Acetylation; D000595:Amino Acid Sequence; D000818:Animals; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D006657:Histones / Q000378:metabolism*; D006801:Humans; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000737:chemistry / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012441:Saccharomyces cerevisiae / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism; D016415:Sequence Alignment; D013091:Spermatogenesis; D013737:Testis / Q000378:metabolism*
chemical_list: C500597:Blm10 protein, S cerevisiae; D006657:Histones; D009687:Nuclear Proteins; C574231:Pa200 protein, mouse; D029701:Saccharomyces cerevisiae Proteins; D046988:Proteasome Endopeptidase Complex