Acetylation-Mediated Proteasomal Degradation of Core Histones during DNA Repair and Spermatogenesis

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• 作者：Min-Xian Qian¹ ; ¹¹ ; Ye Pang¹ ; ¹¹ ; Cui Hua Liu¹ ; ² ; ¹¹ ; Kousuke Haratake⁵ ; ¹¹ ; Bo-Yu Du⁶ ; ¹¹ ; Dan-Yang Ji¹ ; ¹¹ ; Guang-Fei Wang¹ ; Qian-Qian Zhu¹ ; Wei Song⁶ ; Yadong Yu⁷ ; Xiao-Xu Zhang¹ ; Hai-Tao Huang⁶ ; Shiying Miao⁶ ; Lian-Bin Chen¹ ; Zi-Hui Zhang¹ ; Ya-Nan Liang¹ ; Shan Liu¹ ; Hwangho Cha¹ ; Dong Yang¹ ; Yonggong Zhai¹ ; Takuo Komatsu⁵ ; Fuminori Tsuruta⁵ ; Haitao Li⁸ ; Cheng Cao⁹ ; Wei Li³ ; Guo-Hong Li⁴ ; Yifan Cheng⁷ ; Tomoki Chiba⁵ ; Linfang Wang⁶ ; Alfred L. Goldberg¹⁰ ; Yan Shen⁶ ; Xiao-Bo Qiu¹ ; ⁶ ; ^{xqiu@bnu.edu.cn}
• 刊名：Cell
• 出版年：2013
• 出版时间：23 May, 2013
• 年：2013
• 卷：153
• 期：5
• 页码：1012-1024
• 全文大小：3058 K

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Summary

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 ¦Á subunit ¦Á4 s/PSMA8 and/or the catalytic ¦Â 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.