| Date |
Friday, November 11th, 2016 (16:00 – 17:00) |
| Room |
7th Floor, Seminar Room 1, IDAC Center for Basic Aging Research |
| Title |
How cells maintain the critical balance between diversity and stability during replication? |
| Speaker |
Robert Fuchs |
| Affiliation |
CNRS, UMR 7258, Marseille (France) |
| Organizer |
Akira Yasui (IDAC Fellow・ext 8465) |
| Abstract |
Lesion tolerance pathways allow cells to perform genome duplication despite the presence of replication-blocking lesions found in DNA. Following transient fork stalling, replication resumes downstream, leaving gaps in the daughter strand opposite of the lesions. The existence and repair of these gaps have been know for decades and is commonly referred to as “post-replicative repair”. This presentation analyses the crosstalk between 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), which is 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 the monitoring of partition between TLS and HDGR in the context of a single replication-blocking lesion present in the E. coli chromosome (Fuchs 2016). Furthermore, our data shows a chronological involvement of lesion tolerance pathways and TLS acting first, followed by HDGR. Compared to HDGR, TLS represents a minor component of lesion tolerance which owes itself 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. |
