Coordination of DNA replication and histone modification by the Rik1-Dos2 complex

Li, F., Martienssen, R. A., Cande, W. Z. (2011) Coordination of DNA replication and histone modification by the Rik1-Dos2 complex. Nature, 475 (7355). 244-U2562. ISSN 0028-0836

URL: http://www.ncbi.nlm.nih.gov/pubmed/21725325
DOI: 10.1038/nature10161

Abstract

Histone modification marks have an important role in many chromatin processes(1,2). During DNA replication, both heterochromatin and euchromatin are disrupted ahead of the replication fork and are then reassembled into their original epigenetic states behind the fork(3,4). How histone marks are accurately inherited from generation to generation is still poorly understood. In fission yeast (Schizosaccharomyces pombe), RNA interference (RNAi)-mediated histone methylation is cell cycle regulated. Centromeric repeats are transiently transcribed in the S phase of the cell cycle and are processed into short interfering RNAs (siRNAs) by the complexes RITS (RNA-induced initiation of transcriptional gene silencing) and RDRC (RNA-directed RNA polymerase complex)(5-7). The small RNAs together with silencing factors-including Dos1 (also known as Clr8 and Raf1), Dos2 (also known as Clr7 and Raf2), Rik1 and Lid2-promote heterochromatic methylation of histone H3 at lysine 9 (H3K9) by a histone methyltransferase, Clr4 (refs 8-13). The methylation of H3K9 provides a binding site for Swi6, a structural and functional homologue of metazoan heterochromatin protein 1 (HP1)(14). Here we characterize a silencing complex in fission yeast that contains Dos2, Rik1, Mms19 and Cdc20 (the catalytic subunit of DNA polymerase-e). This complex regulates RNA polymerase II (RNA Pol II) activity in heterochromatin and is required for DNA replication and heterochromatin assembly. Our findings provide a molecular link between DNA replication and histone methylation, shedding light on how epigenetic marks are transmitted during each cell cycle.

Item Type: Paper
Uncontrolled Keywords: fission yeast schizosaccharomyces-pombe polymerase-epsilon rna interference s-phase heterochromatin formation chromosomal replication epigenetic inheritance cell-cycle chromatin
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA methylation
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > DNA replication
organism description > yeast > Saccharomyces
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > epigenetics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > epigenetics

bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > siRNA
CSHL Authors:
Communities: CSHL Cancer Center Program > Gene Regulation and Cell Proliferation
CSHL Cancer Center Shared Resources > DNA Sequencing Service
CSHL Cancer Center Shared Resources > Proteomics Service
CSHL labs > Martienssen lab
CSHL Cancer Center Shared Resources > Mass Spectrometry Service
Depositing User: CSHL Librarian
Date Deposited: 14 Oct 2011 13:46
Last Modified: 30 Oct 2015 14:41
PMCID: PMC3163161
Related URLs:
Dataset ID:
  • GeneBank: JN388396
  • GeneBank: JN388397
  • GeneBank: JN388396
  • GeneBank: JN388396
  • GEO: GSE308
URI: http://repository.cshl.edu/id/eprint/15558

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