Details

Autor(en) / Beteiligte

• Qian, Min-Xian
• Pang, Ye
• Liu, Cui Hua
• Haratake, Kousuke
• Du, Bo-Yu
• Ji, Dan-Yang
• Wang, Guang-Fei
• Zhu, Qian-Qian
• Song, Wei
• Yu, Yadong
• Zhang, Xiao-Xu
• Huang, Hai-Tao
• Miao, Shiying
• Chen, Lian-Bin
• Zhang, Zi-Hui
• Liang, Ya-Nan
• Liu, Shan
• Cha, Hwangho
• Yang, Dong
• Zhai, Yonggong
• Komatsu, Takuo
• Tsuruta, Fuminori
• Li, Haitao
• Cao, Cheng
• Li, Wei
• Li, Guo-Hong
• Cheng, Yifan
• Chiba, Tomoki
• Wang, Linfang
• Goldberg, Alfred L.
• Shen, Yan
• Qiu, Xiao-Bo

Titel

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

Ist Teil von

• Cell, 2013-05, Vol.153 (5), p.1012-1024

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2013

Link zum Volltext

Quelle

Free E-Journal (出版社公開部分のみ）

Beschreibungen/Notizen

• 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. [Display omitted] •Most proteasomes in mammalian testes are “spermatoproteasomes” that contain PA200•Deletion of PA200 in mice delays core histone disappearance in elongated spermatids•PA200/Blm10 promotes degradation of acetyl-histones during somatic DNA damage•Binding of histones to bromodomain-like regions in PA200/Blm10 depends on acetylation Specialized proteasomes containing the protein PA2000/BLm10 catalyze the degradation of acetylated—rather than ubiquitinated—core histones during spermatogenesis and DNA damage repair.