セミナー情報
Interplay and genetic control of Translesion Synthesis and Damage Avoidance pathways in E. coli.(Dr. Robert P. Fuchs)
RecG controls DNA amplification at double-strand breaks and arrested replication forks.(Professor David Leach)
| 演題 | Interplay and genetic control of Translesion Synthesis and Damage Avoidance pathways in E. coli.(Dr. Robert P. Fuchs) RecG controls DNA amplification at double-strand breaks and arrested replication forks.(Professor David Leach) |
| 講演者 | Dr. Robert P. Fuchs, CRCM, CNRS Marseille (France) Professor David Leach, Institute of Cell Biology, School of Biological Sciences, University of Edinburgh (UK) |
| 使用言語 | English |
| 日時 | 2016年11月18日(金曜日) 14：30～16：30 |
| 場所 | Bio Large seminar room |
| 内容 | 【Interplay and genetic control of Translesion Synthesis and Damage Avoidance pathways in E. coli】 Lesion tolerance pathways allow cellso pathways exhibit a common a key in E. coli chromosome (Fuchs 2016). Our data show a chronological involvement of lesion tolerance pathways, TLS acting first followed by HDGR. Compared to DA, 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 DA is thus set by mere sequestration of the TLS substrates into early recombination intermediates. We will show that DA is essentially mediated by Homology Directed Gap Repair in a RecA dependent manner (Laureti et al. 2015). Surprisingly, when homologous recombination is impaired (recA mutant) or when wild type cells occasionally fail to repair this gap, cells are still able to divide at the expense of losing the non-repaired chromatid, thus ensuring cell survival and proliferation. Fuchs RP. 2016. Tolerance of lesions in E. coli: Chronological competition between Translesion Synthesis and Damage Avoidance. DNA Repair (Amst) 44: 51–58. Laureti L, Demol J, Fuchs RP, Pagès V. 2015. Bacterial Proliferation: Keep Dividing and Don't Mind the Gap. PLoS Genet 11: e1005757. Naiman K, Pagès V, Fuchs RP. 2016. A defect in homologous recombination leads to increased translesion synthesis in E. coli. Nucleic Acids Res. 【RecG controls DNA amplification at double-strand breaks and arrested replication forks】 DNA amplification is a powerful mutational mechanism that is a hallmark of cancer and drug resistance. It is therefore important to understand the fundamental pathways that cells employ to avoid over-replicating sections of their genomes. Recent studies demonstrate that, in the absence of Escherichia coli RecG, DNA amplification is observed at sites of DNA double-strand break repair and of DNA replication arrest that are processed to generate double-strand ends. RecG also plays a role in stabilising joint molecules formed during DNA double-strand break repair. We propose that in the absence of RecG the generation of DNA double-strand ends from incorrect loading of the replicative helicase at D-loops formed by recombination, and at arrested replication forks provides a previously unrecognised mechanism of DNA amplification. |
| 問合せ先 | 原核生物分子遺伝学 真木 壽治 (maki@bs.naist.jp) |