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Mechanism of broken replication fork repair

日期: 2014-11-07
金沙威尼斯欢乐娱人城
2014学年秋季学期系列学术讲座之七
Title:Mechanism of broken replication fork repair
Speaker:Grzegorz Ira, Ph.D.
Associate Professor
Molecular and Human Genetics
Baylor College of Medicine
Houston, TX, US
Time:2014年11月7日(星期五)13:00-14:30
Place:金沙威尼斯欢乐娱人城二教109
Host: 孔道春(电话:62760866)
Abstract:
DNA double strand breaks (DSBs) are detrimental to cells when unrepaired or repaired incorrectly. Many DSBs arise when a replication fork encounters a nick, resulting in a single-ended DSB (seDSB). Two related Break Induced Replication (BIR) pathways were proposed for the repair of broken forks that differ in processing of the D-loop, the initial recombination intermediate formed after 3strand invasion. In the first pathway, the D-loop is extended by polymerase d/Pol32 and Pif1 helicase. This migrating D-loop BIR (MD-BIR) mechanism was studied outside the context of replication forks, and was shown to be highly mutagenic and prone to template switches even far from the DNA breakage site. The second pathway involves D-loop resolution (DR-BIR) by structure specific nucleases to reestablish a replication fork. To ascertain the contribution of these two mechanisms in repair of broken replication forks we studied the repair of a Flp-nick induced seDSBs at several loci within the yeast genome either between two origins of replication or between an origin and a telomere. Further we estimated the rates of mutations and template switches at different position with respect to broken replication fork. I will discuss (i) the role of MD-BIR and DR-BIR in repair of broken replication forks, (ii) enzymatic requirements for the repair of the broken forks, (iii) contribution of converging fork to repair and (iv) fidelity of broken fork repair.

欢迎各位老师同学积极参加!