2. Academic Validation
  3. Acetylation-mediated proteasomal degradation of core histones during DNA repair and spermatogenesis

Acetylation-mediated proteasomal degradation of core histones during DNA repair and spermatogenesis

  • Cell. 2013 May 23;153(5):1012-24. doi: 10.1016/j.cell.2013.04.032.
Min-Xian Qian 1,  Ye Pang,  Cui Hua Liu,  Kousuke Haratake,  Bo-Yu Du,  Dan-Yang Ji,  Guang-Fei Wang,  Qian-Qian Zhu,  Wei Song,  Yadong Yu,  Xiao-Xu Zhang,  Hai-Tao Huang,  Shiying Miao,  Lian-Bin Chen,  Zi-Hui Zhang,  Ya-Nan Liang,  Shan Liu,  Hwangho Cha,  Dong Yang,  Yonggong Zhai,  Takuo Komatsu,  Fuminori Tsuruta,  Haitao Li,  Cheng Cao,  Wei Li,  Guo-Hong Li,  Yifan Cheng,  Tomoki Chiba,  Linfang Wang,  Alfred L Goldberg,  Yan Shen,  Xiao-Bo Qiu
Affiliations

Affiliation

  • 1 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.
PMID: 23706739 DOI: 10.1016/j.cell.2013.04.032
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.

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