Biology Reference
In-Depth Information
remodeling may occur by formation of a bulge of DNA on the surface of the
nucleosome that can be extended by translocation to form a larger loop, which
upon dissipation can result in reverse translocation, a jump in the position of
the nucleosome, or nucleosome sliding.
C.
Functions
RSC is important for transcriptional control of many genes in
S. cerevisiae
and co-immunoprecipitated with all three RNA polymerases.
29,31,56
It can act
to both activate and repress transcription of a group of genes that are distinct
from those regulated by SWI/SNF.
26,29,57
ChIP on chip analysis of the genome-
wide localization of the RSC complex identified RSC binding at
In Vivo
700 pro-
moters (
11% of genes), and no difference was seen in the Rsc1 and Rsc2
profiles.
56
Furthermore, around 12% of RNA polymerase II-transcribed genes
were up- or downregulated at least twofold in an
rsc4
mutant strain.
31
RSC was
bound at a number of tRNA promoters transcribed by RNA polymerase III and
was enriched at many genes involved in mitochondrial function, nitrogen and
carbon metabolism, and histone promoters.
Transcripts of genes affecting cell wall integrity, cell cycle control, and
spindle pole body formation were misregulated in
rsc
mutants, despite not
having enriched levels of RSC at their promoters by ChIP-chip, and transcrip-
tion of some genes with RSC bound at their promoters is unaffected in
rsc
mutants.
29
This demonstrates that the correlation between promoter binding
and transcriptional regulation is not a simple one and that different RSC sub-
units have different effects on transcription. More recently, a putative Rsc3
sequence-specific binding site has been identified approximately 100 bp up-
stream of the transcription start site of 708 genes (169 of which are essential)
and Rsc3 has been connected with nucleosome exclusion from the promoters of
these genes.
30
In vitro
, RSC was also able to facilitate passage of RNA polymer-
ase II through acetylated nucleosomes.
58
To date, none of the known DNA
repair genes have been identified as being transcriptionally controlled by RSC.
In addition to transcription, the RSC complex has been shown to be
important for proper kinetochore function, adaptation to the spindle assembly
checkpoint, plasmid and chromosome maintenance, correct localization of the
nuclear pore complex, meiotic sporulation, and sister chromatid cohesion (dis-
cussed later).
59-65
Furthermore, progression through the cell cycle is affected in
rsc
mutants. Cell cycle arrest at the G2/M checkpoint occurs in strains contain-
ing either a deletion, a ts allele, or a degron allele of genes encoding a number of
RSC subunits (Sth1, Sfh1, Rsc3, Rsc4, Rsc6, Rsc8, Rsc9, Rsc58),
26,28,29,66-68
while loss of Sth1 or Htl1 function promotes polyploidy.
26,66,68,69
The RSC complex was first implicated in the DNA damage response
upon the finding that deletion of several of the nonessential subunits of RSC
(
rsc1
,
rsc2
,
rsc7
,
rsc30
,
htl1
) or temperature-sensitive mutations in Sth1 confer
