Dicer Promotes Transcription Termination at Sites of Replication Stress to Maintain Genome Stability

Castel, Stephane E, Ren, Jie, Bhattacharjee, Sonali, Chang, An-Yun, Sánchez, Mar, Valbuena, Alberto, Antequera, Francisco, Martienssen, Robert A (October 2014) Dicer Promotes Transcription Termination at Sites of Replication Stress to Maintain Genome Stability. Cell, 159 (3). pp. 572-583. ISSN 0092-8674

Abstract

Summary Nuclear RNAi is an important regulator of transcription and epigenetic modification, but the underlying mechanisms remain elusive. Using a genome-wide approach in the fission yeast S. pombe, we have found that Dcr1, but not other components of the canonical RNAi pathway, promotes the release of Pol II from the 3′ end of highly transcribed genes, and, surprisingly, from antisense transcription of rRNA and tRNA genes, which are normally transcribed by Pol I and Pol III. These Dcr1-terminated loci correspond to sites of replication stress and DNA damage, likely resulting from transcription-replication collisions. At the rDNA loci, release of Pol II facilitates DNA replication and prevents homologous recombination, which would otherwise lead to loss of rDNA repeats especially during meiosis. Our results reveal a novel role for Dcr1-mediated transcription termination in genome maintenance and may account for widespread regulation of genome stability by nuclear RNAi in higher eukaryotes.

Item Type: Paper
Subjects: bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > transcription
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > RNAi
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > dicer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > dicer
CSHL Authors:
Communities: CSHL labs > Martienssen lab
School of Biological Sciences > Publications
CSHL Cancer Center Program > Gene Regulation and Cell Proliferation
Depositing User: Matt Covey
Date: 23 October 2014
Date Deposited: 24 Oct 2014 15:04
Last Modified: 16 Jul 2021 16:21
PMCID: PMC4243041
Related URLs:
URI: https://repository.cshl.edu/id/eprint/30871

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