| First Author | Feng L | Year | 2012 |
| Journal | Nat Struct Mol Biol | Volume | 19 |
| Issue | 2 | Pages | 201-6 |
| PubMed ID | 22266820 | Mgi Jnum | J:192582 |
| Mgi Id | MGI:5465398 | Doi | 10.1038/nsmb.2211 |
| Citation | Feng L, et al. (2012) The E3 ligase RNF8 regulates KU80 removal and NHEJ repair. Nat Struct Mol Biol 19(2):201-6 |
| abstractText | The ubiquitination cascade has a key role in the assembly of repair and signaling proteins at sites of double-strand DNA breaks. The E3 ubiquitin ligase RING finger protein 8 (RNF8) triggers the initial ubiquitination at double-strand DNA breaks, whereas sustained ubiquitination requires the downstream E3 ligase RING finger protein 168 (RNF168). It is not known whether RNF8 and RNF168 have discrete substrates and/or form different ubiquitin chains. Here we show that RNF168 acts with the ubiquitin-conjugating enzyme E2 13 (UBC13) and specifically synthesizes Lys63-linked chains, whereas RNF8 primarily forms Lys48-linked chains on chromatin, which promote substrate degradation. We also find that RNF8 regulates the abundance of the nonhomologous end-joining (NHEJ) repair protein KU80 at sites of DNA damage, and that RNF8 depletion results in prolonged retention of KU80 at damage sites and impaired nonhomologous end-joining repair. These findings reveal a distinct feature of RNF8 and indicate the involvement of the ubiquitination-mediated degradation pathway in DNA damage repair. |
