| First Author | Qian MX | Year | 2013 |
| Journal | Cell | Volume | 153 |
| Issue | 5 | Pages | 1012-24 |
| PubMed ID | 23706739 | Mgi Jnum | J:197675 |
| Mgi Id | MGI:5494329 | Doi | 10.1016/j.cell.2013.04.032 |
| Citation | Qian MX, et al. (2013) Acetylation-Mediated Proteasomal Degradation of Core Histones during DNA Repair and Spermatogenesis. Cell 153(5):1012-24 |
| abstractText | 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 alpha subunit alpha4 s/PSMA8 and/or the catalytic beta 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. |
