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Epigenetic instability due to defective replication of structured DNA.

Molecular cell (2010-12-15)
Peter Sarkies, Charlie Reams, Laura J Simpson, Julian E Sale
ABSTRACT

The accurate propagation of histone marks during chromosomal replication is proposed to rely on the tight coupling of replication with the recycling of parental histones to the daughter strands. Here, we show in the avian cell line DT40 that REV1, a key regulator of DNA translesion synthesis at the replication fork, is required for the maintenance of repressive chromatin marks and gene silencing in the vicinity of DNA capable of forming G-quadruplex (G4) structures. We demonstrate a previously unappreciated requirement for REV1 in replication of G4 forming sequences and show that transplanting a G4 forming sequence into a silent locus leads to its derepression in REV1-deficient cells. Together, our observations support a model in which failure to maintain processive DNA replication at G4 DNA in REV1-deficient cells leads to uncoupling of DNA synthesis from histone recycling, resulting in localized loss of repressive chromatin through biased incorporation of newly synthesized histones.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
ChIPAb+ Acetyl-Histone H3 - ChIP Validated Antibody and Primer Set, from rabbit
Sigma-Aldrich
Anti-acetyl-Histone H4 Antibody, 1 mg/mL, Upstate®
Sigma-Aldrich
ChIPAb+ Dimethyl-Histone H3 (Lys9) - ChIP Validated Antibody and Primer Set, serum, from rabbit
Sigma-Aldrich
ChIPAb+ Acetyl-Histone H4 - ChIP Validated Antibody and Primer Set, serum, from rabbit