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

• Published in: Nature (London) Vol. 479; no. 7371; pp. 135 - 138
• Main Authors: ZARATIEGUI, Mikel, CASTEL, Stephane E, ZACHEUS CANDE, W, ANTEQUERA, Francisco, ARCANGIOLI, Benoit, MARTIENSSEN, Robert A, IRVINE, Danielle V, KLOC, Anna, JIE REN, FEI LI, DE CASTRO, Elisa, MARIN, Laura, CHANG, An-Yun, GOTO, Derek
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group 03.11.2011
• Subjects: Arrests; Biochemistry, Molecular Biology; Biological and medical sciences; Centromere; Centromere - genetics; Centromere - metabolism; Chromatin; Chromosomal Proteins, Non-Histone; Chromosomal Proteins, Non-Histone - genetics; Chromosomal Proteins, Non-Histone - metabolism; Cloning; DNA Damage; DNA methylation; DNA Replication; DNA Replication - physiology; DNA-Directed DNA Polymerase; DNA-Directed DNA Polymerase - metabolism; Enzymes; Fundamental and applied biological sciences. Psychology; Gene Silencing; Genetic testing; Genetics; Heterochromatin; Heterochromatin - genetics; Heterochromatin - metabolism; Histones; Histones - metabolism; Homologous Recombination; Kinases; Life Sciences; Models, Genetic; Molecular and cellular biology; Molecular genetics; Molecular Sequence Data; Physiological aspects; Proteins; Replication; Replication Origin; RNA Interference; RNA polymerase; RNA Polymerase II; RNA Polymerase II - metabolism; RNA polymerases; RNA, Small Interfering; RNA, Small Interfering - genetics; RNA, Small Interfering - metabolism; S Phase; Schizosaccharomyces; Schizosaccharomyces - genetics; Schizosaccharomyces pombe Proteins; Schizosaccharomyces pombe Proteins - genetics; Schizosaccharomyces pombe Proteins - metabolism; Transcription, Genetic; Transfer RNA; Yeast; France; United States; Gene silencing; Replication; Heterochromatin; RNA interference; RNA; RNA polymerase II
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/nature10501

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.