RRC ID 12570
Author Li F, Martienssen R, Cande WZ.
Title Coordination of DNA replication and histone modification by the Rik1-Dos2 complex.
Journal Nature
Abstract Histone modification marks have an important role in many chromatin processes. 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. 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). 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). Here we characterize a silencing complex in fission yeast that contains Dos2, Rik1, Mms19 and Cdc20 (the catalytic subunit of DNA polymerase-ε). 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.
Volume 475(7355)
Pages 244-8
Published 2011-7-3
DOI 10.1038/nature10161
PII nature10161
PMID 21725325
PMC PMC3163161
MeSH Cdc20 Proteins Cell Cycle / genetics Cell Cycle / physiology Cell Cycle Proteins / metabolism Chromosomal Proteins, Non-Histone / metabolism* Chromosomes, Fungal / chemistry Chromosomes, Fungal / genetics Chromosomes, Fungal / metabolism DNA Replication / physiology* Epigenesis, Genetic Gene Expression Regulation, Fungal Gene Silencing Heterochromatin / chemistry Heterochromatin / genetics Heterochromatin / metabolism Histones / chemistry Histones / metabolism* Lysine / metabolism Methylation Multiprotein Complexes / chemistry Multiprotein Complexes / metabolism RNA Interference RNA Polymerase II / metabolism RNA, Small Interfering Schizosaccharomyces / cytology Schizosaccharomyces / genetics* Schizosaccharomyces / metabolism* Schizosaccharomyces pombe Proteins / metabolism* Transcription Factors / metabolism Transcription, Genetic
IF 41.577
Times Cited 61
Yeast FY14792