Biology Reference
In-Depth Information
Nhp10 (an HMG-like subunit of the Ino80 complex) and
g
-H2AX, and the loss
of either component leads to compromised DSB repair.
313
However, two con-
flicting observations were reported with respect to recruitment of repair medi-
ators at the DSB. One group observed that resection of 5
0
strands at the break
was compromised in Arp8 and H2A mutants,
328
while the other reported that
even though the resection occurred regularly in the
Ino80
mutant, Rad51
recruitment was delayed.
364
The SWI/SNF chromatin-remodeling complex was first identified in two
genetic screens in budding yeast (
Tabl e I
). The first gene regulates the mating
type switch (SWI) and the other regulates sucrose nonfermenting (SNF) phe-
notypes.
383-385
The multisubunit complex consists of 9-12 subunits and has
shown to possess ATP-dependent chromatin-remodeling activity
in vitro
.
386,387
Several homologs of SWI/SWF have been identified in metazoans; for example,
in
Drosophila
, BRM (Brahma) and BAPs (BRM-associated proteins) were char-
acterized as SWI/SNF homologs and in humans, BRM, BRG1 (Brahma-related
gene 1) and BAFs (BRM- or BRG1-associated factors) are found as SWI/SNF
complexes.
73,388-390
SWI/SNF remodels nucleosomes both by nucleosome slid-
ing and nucleosome ejection.
391
Itsactivityisimplicatedbothintranscription
and DSB repair.
362,366,367
SWI/SNF involvement in DSB repair is extensively
studied in yeast. Although Rad51 NPF formation does not require
chromatin remodelers for homology searches and capture even on positioned
nucleosomal surfaces
in vivo
or
in vitro
,
156,282,373,392
Swi/Snf remodelers
are essential for recombinational repair within heterochromatin.
365
When
nucleosomal donor sequences are constrained by Sir2, Sir3, and Sir4
structural proteins that are found at telomeres and silent
MAT
loci,
remodeling activity of Swi/Snf was required for efficient joint molecule
formation.
365
Interestingly, Rad54, Ino80, RSC, and Swr1 were incapable of
promoting joint molecule formation within heterochromatin.
365
Several
mammalian SWI/SNF complexes have also been shown to interact with
DSB repair response proteins such as BRCA1, p53, and with FA pathway
proteins.
393-395
Remodel structure of chromatin (RSC) is another multisubunit ATP-
dependent chromatin remodeler that is rapidly recruited to the DSB site
upon damage.
366
It is homologous to the SWI/SNF complex.
372
Its rapid
recruitment to DSB that coincides with MRX recruitment suggests that initial
nucleosome remodeling at the DSB might facilitate DNA end-processing by
the MRX complex.
362,368,369
RSC is also required for loading of cohesins during
DSB repair to ensure that repair occurs between sister chromatids during
mitotic HR repair.
368,370
However, there is also evidence that suggests that
RSC might be involved in the latter stages of HR repair pathway, particularly
during the DNA ligation step after DNA synthesis.
366
