Abstract
Heterochromatin comprises tightly compacted repetitive regions of eukaryotic chromosomes. The inheritance of heterochromatin through mitosis requires RNA interference (RNAi), which guides histone modification1 during the DNA replication phase of the cell cycle2. Here we show that the alternating arrangement of origins of replication and non-coding RNA in pericentromeric heterochromatin results in competition between transcription and replication in Schizosaccharomyces pombe. Co-transcriptional RNAi releases RNA polymerase II (Pol II), allowing completion of DNA replication by the leading strand DNA polymerase, and associated histone modifying enzymes3 that spread heterochromatin with the replication fork. In the absence of RNAi, stalled forks are repaired by homologous recombination without histone modification.
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Accession codes
Primary accessions
GenBank/EMBL/DDBJ
Gene Expression Omnibus
Data deposits
Genomics data and analysis are available from the Gene Expression Omnibus accession number GSE30837. Individual cDNA sequences are available from GenBank with accession numbers JN388396–JN388565.
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Acknowledgements
We thank D. Roh and T. Volpe for isolating cDNA clones. D.V.I. was supported by a NHMRC CJ Martin Postdoctoral Research Fellowship. M.Z. was supported by a fellowship from the Spanish Ministry of Science. This work was supported by grants BFU2008-01919 and Consolider-Ingenio CSD2007-00015 from the Spanish Ministry of Science and Innovation to F.A., and NIH R01 GM076396 to W.Z.C. and R.A.M.
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S.C., D.V.I., A.K., J.R. contributed equally to this work and are listed in alphabetical order. M.Z., S.C., D.V.I., A.K., J.R., F.L., E.d.C., L.M., A.-Y.C. and D.G. performed experiments, and S.C. analysed the data. W.Z.C., F.A., B.A. and R.A.M. designed experiments and R.A.M. and M.Z. wrote the manuscript.
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Zaratiegui, M., Castel, S., Irvine, D. et al. RNAi promotes heterochromatic silencing through replication-coupled release of RNA Pol II. Nature 479, 135–138 (2011). https://doi.org/10.1038/nature10501
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DOI: https://doi.org/10.1038/nature10501
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