| Literature DB >> 26994443 |
Shunsuke Kobayashi1, Islam Shamima Keka1, Guillaume Guilbaud2, Julian Sale2, Takeo Narita3, H Ismail Abdel-Aziz4, Xin Wang1, Saki Ogawa1, Hiroyuki Sasanuma1, Roland Chiu5, Vibe H Oestergaard6, Michael Lisby6, Shunichi Takeda7.
Abstract
The replicative DNA polymerases are generally blocked by template DNA damage. The resulting replication arrest can be released by one of two post-replication repair (PRR) pathways, translesion DNA synthesis (TLS) and template switching by homologous recombination (HR). The HERC2 ubiquitin ligase plays a role in homologous recombination by facilitating the assembly of the Ubc13 ubiquitin-conjugating enzyme with the RNF8 ubiquitin ligase. To explore the role of HERC2 and RNF8 in PRR, we examined immunoglobulin diversification in chicken DT40 cells deficient in HERC2 and RNF8. Unexpectedly, the HERC2(-/-) and RNF8(-/-) cells and HERC2(-/-)/RNF8(-/-) double mutant cells exhibit a significant reduction in the rate of immunoglobulin (Ig) hypermutation, compared to wild-type cells. Further, the HERC2(-/-) and RNF8(-/-) mutants exhibit defective maintenance of replication fork progression immediately after exposure to UV while retaining proficient post-replicative gap filling. These mutants are both proficient in mono-ubiquitination of PCNA. Taken together, these results suggest that HERC2 and RNF8 promote TLS past abasic sites and UV-lesions at or very close to stalled replication forks.Entities:
Keywords: HERC2; Post-replication repair; RNF8; Translesion DNA synthesis; Ubiquitination
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Year: 2016 PMID： 26994443 PMCID： PMC5351851 DOI： 10.1016/j.dnarep.2016.02.002
Source DB: PubMed Journal: DNA Repair (Amst) ISSN： 1568-7856