Biology Reference
In-Depth Information
these gene products have been shown to have synthetic lethal interactions.
405
It
is suggested that once RAD54 removes the RAD51 from the 3
0
-end of
the invading strand, HELQ-1 and RFS-1 might be involved in removing the
remaining RAD51 from the heteroduplex DNA.
405,406
VIII. Second-End Capture
When the RAD51 NPF forms a D-loop, the displaced strand can poten-
tially pair with the second 3
0
overhang that is produced. This process is called
second-end capture. In yeast and mammalian cells, this process is mediated by
RAD52 through its inherent ability of pair with RPA-coated ssDNA.
166,407-409
In
U. maydis
, Brh2 is also capable of catalyzing second-end capture in condi-
tions where annealing by RAD52 is inhibited.
217
IX. dHJ Dissolution
In the classical DSB repair model, after the second-end capture, DNA
synthesis and ligation result in a dHJ, which can be either dissolved or resolved.
During mitotic recombinational repair, the former is the preferred path-
way.
29,34,410
dHJ dissolution is mainly mediated by RecQ helicases (
Table I
;
Ref.
410
). The budding yeast RecQ homolog Sgs1 (fission yeast Rqh1) interacts
strongly with the Top3 topoisomerase.
411-414
In human cells, the homologous
RecQ helicase BLM strongly interacts with TOP3
a
.
415,416
This helicase-
topoisomerase complex has been shown to interact with yeast Rmi1/ Nce4
(RMI1/ BLAP75 in human cells) DNA-binding protein. In budding yeast, dHJ
dissolution is mediated by Sgs1-Top3-Rmi1.
417,418
In human cells, the
dHJ dissolution complex is comprised of BLM-TOP3
a
-RMI1-RMI2.
410,419
X. Holliday Junction Resolution
Weisberg and colleagues reported the first biochemical evidence for an
enzyme that has Holliday junction resolution activity in 1982. They identified
the T4-endonuclease activity of bacteriophage T4 that was capable of cutting the
branched structures of the phage genome before it was packaged into new phage
particles.
420-423
Soon afterwards, Holliday junction resolvases were identified in
several organisms including budding yeast mitochondrial Cce1 (from cell-free
extracts), fission yeast Ydc2, and endonuclease I of the bacteriophage T7.
424-429
The first prokaryotic resolvase to be identified was
Escherichia coli
RuvC.
430,431
Biochemical characterization of RuvC revealed that the resolvase binds the
