| 日時： | 平成28年11月11日（金）午後４時～5時 |
| 場所： | 加齢研実験研究棟７階 セミナー室1 |
| 演題： | 細胞は如何に複製をのりこえるか？ |
| 講師： | ロベルト フックス |
| 所属： | CNRS, UMR 7258, Marseille (France) |
| 担当： | 安井 明（所属 加齢研フェロー研究室・内線 8465 ） |
| 要旨： | Lesion tolerance pathways allow cells to perform genome duplication despite the presence of replication-blocking lesions in DNA. Following transient fork stalling, replication resumes downstream leaving daughter strand gaps opposite lesions. The existence and repair of these gaps has been know for decades and is commonly referred to as post-replicative repair. This presentation analyses the crosstalk between the pathways involved in the repair of these gaps. A key repair intermediate is formed when RecA protein binds to these gaps forming ssDNA.RecA filaments turning on the so-called SOS signal. Gaps are either “repaired” by Translesion Synthesis (TLS) a process involving the transient recruitment of a specialized DNA polymerase that copies across the lesion with an intrinsic risk of fixing a mutation or by Damage Avoidance, an error-free pathway that involves homologous recombination with the sister chromatid (Homology Directed Gap Repair: HDGR). We have developed a methodology that allows monitor the partition between TLS and HDGR in the context of a single replication-blocking lesion present in the E. coli chromosome (Fuchs 2016). Our data show a chronological involvement of lesion tolerance pathways, TLS acting first followed by HDGR. Compared to HDGR, TLS represents a minor component of lesion tolerance owing to the generally poor enzymatic activity of the specialized DNA polymerases and to their controlled level of expression. Chronology is achieved in view of the fact that the TLS substrate, i.e. the ssDNA.RecA filament, persists for only a limited amount of time before the RecA filament engages into an early recombination intermediates (D-loop) with the sister chromatid (Naiman et al. 2016). Time-based competition between TLS and HDGR is thus set by mere sequestration of the TLS substrates into early recombination intermediates. Fuchs RP. Tolerance of lesions in E. coli: Chronological competition between Translesion Synthesis and Damage Avoidance. DNA Repair (Amst) 2016 44: 51–58.Naiman K, Pagès V, Fuchs RP. A defect in homologous recombination leads to increased translesion synthesis in E. coli. Nucleic Acids Res 2016 2016, 44: 7691–7699 |
