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RNAi promotes heterochromatic silencing through replication-coupled release of RNA Pol II.

Heterochromatin comprises tightly compacted repetitive regions of eukaryotic chromosomes. The inheritance of heterochromatin through mitosis requires RNA interference (RNAi), which guides histone modification during the DNA replication phase of the cell cycle. 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 enzymes that spread heterochromatin with the replication fork. In the absence of RNAi, stalled forks are repaired by homologous recombination without histone modification.

Pubmed ID: 22002604

Authors

  • Zaratiegui M
  • Castel SE
  • Irvine DV
  • Kloc A
  • Ren J
  • Li F
  • de Castro E
  • MarĂ­n L
  • Chang AY
  • Goto D
  • Cande WZ
  • Antequera F
  • Arcangioli B
  • Martienssen RA

Journal

Nature

Publication Data

November 3, 2011

Associated Grants

  • Agency: NIGMS NIH HHS, Id: R01 GM076396
  • Agency: NIGMS NIH HHS, Id: R01 GM076396
  • Agency: NIGMS NIH HHS, Id: R01 GM076396-04

Mesh Terms

  • Centromere
  • Chromosomal Proteins, Non-Histone
  • DNA Damage
  • DNA Replication
  • DNA-Directed DNA Polymerase
  • Gene Silencing
  • Heterochromatin
  • Histones
  • Homologous Recombination
  • Models, Genetic
  • Molecular Sequence Data
  • RNA Interference
  • RNA Polymerase II
  • RNA, Small Interfering
  • Replication Origin
  • S Phase
  • Schizosaccharomyces
  • Schizosaccharomyces pombe Proteins
  • Transcription, Genetic