Biology Reference
In-Depth Information
Loss of one chromatid arm
5
¢
-3
¢
Resection
5
¢
-3
¢
Resection
Telomere uncapping
D-loop formation & DNA synthesis
Cleavage of D-loop & ligation
DNA synthesis
DNA synthesis
F
IG
. 3. Break-induced replication (BIR) initiates from a single-ended strand invasion. If one
arm of the chromatid is lost after the double-strand break (DSB) or if a telomere is uncapped, a 3
0
overhang is formed. DNA synthesis can continue to the end of the chromatid either by migration of
the D-loop or after D-loop cleavage.
products for viability.
54,55
Uncontrolled HR, however, during replication fork
collapse can lead to gross genomic instability. These observations suggest that
cell cycle checkpoints tightly regulate the HR pathway to ensure genomic
integrity.
54,55
If the nascent strand encounters a nick during replication, the fork may stall
and the incomplete replicated strand may undergo resection, which can invade
the sister chromatid once the latter is ligated (
Fig. 4
, left). After DNA synthesis,
a resulting partial Holliday junction may be resolved to reinitiate DNA synthe-
sis at the fork. If the leading strand stalls due to a lesion on its template, the
newly synthesized strands may pair up via reverse branch migration to form a
chicken-foot structure (a pseudo-Holliday junction;
Fig. 4
, middle; Ref.
56
).
Following a short DNA synthesis to fill in the chicken-foot ssDNA tail,
the replication fork may be reinitiated by forward branch migration. A lesion
on the lagging strand template would lead to a template switch mechanism
