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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:英国威廉希尔公司二教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 3’ strand 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.
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