Biology Reference
In-Depth Information
to sites of damage and inefficient DNA repair. These findings demonstrate a
direct role for GCN5 and E2F1 in NER involving H3K9 acetylation and
increased accessibility to the NER machinery.
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Histone methylation occurs on lysine and arginine side chains but does not
alter the charge on histone protein as done by acetylation and phosphorylation.
Not much research has been done to find the role of histone methylation in
NER in humans, but one study has shown that lysine methylation in histones is
required for efficient NER in
S. cerevisiae
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Although phosphorylation is important for some histones and DNA repair
pathways, there are still no studies which clearly prove some role of histone
phosphorylation on NER. One study showed that histone H2A phosphoryla-
tion controls Crb2 (a cell cycle checkpoint protein) recruitment at DNA
breaks, maintains checkpoint arrest, and influences DNA repair in fission
yeast.
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Another study on human primary fibroblasts proposed that histone
H2AX phosphorylation occurs after UV-induced NER starts operating.
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As described for other DNA repair pathways, monoubiquitylation of his-
tones happens in NER. UV-induced monoubiquitylation of H2A is dependent
on functional NER and occurs after incision of the damaged strand.
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Howev-
er, although this modification has been shown to occur at UV, it still has to be
seen how this modification affects the process of NER.
IV. Histone Modifications of Base Excision Repair
Base excision repair (BER) is the primary DNA repair pathway that corrects
base lesions that arise due to oxidation, alkylation, deamination, and depurina-
tiation/depyrimidination damage. BER facilitates the repair of damaged DNA
via two general pathways: short and long patch. The short-patch BER pathway
leads to a repair tract of a single nucleotide. Alternatively, the long-patch BER
pathway produces a repair tract of at least two nucleotides. The BER pathway is
initiated by one of many DNA glycosylases, which recognize and catalyze the
removal of damaged bases. The completion of the BER pathway is accom-
plished by the coordinated action of at least three additional enzymes. These
downstream enzymes carry out strand incision, gap filling, and ligation.
There are only a few studies published about covalent histone modification
in BER pathways. Though several repair factors involved in BER pathways,
such as Fen1, DNA-polymerase-
b
, and TDG, are
in vitro
and
in vivo
substrates
for phosphorylation and acetylation,
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phosphorylation, methylation, or
acetylation of histones in BER pathways has not been reported so far.
However, for BER, there are many studies that indicate that histones are
covalently modified by mono(ADP)-ribose in response to DNA damage. It has
been shown that when cells were exposed to damage by
OH radicals or
