New Role for RNA Interference During Chromosomal Replication Discovered
ScienceDaily (Oct. 16, 2011) — At the same time that a cell's DNA gets duplicated, a third of it gets super-compacted into repetitive clumps called heterochromatin. This dense packing serves to repress or "silence" the DNA sequences within -- which could wreck the genome if activated -- as well as regulate the activity of nearby genes. When the cell divides, the daughter cells not only inherit a copy of the mother cell's DNA, but also the exact pattern in which that DNA is clumped into heterochromatin.
This "epigenetic" mode of inheritance -- information not transmitted through the DNA code itself but by the way in which it is packaged -- has long been investigated by Cold Spring Harbor Laboratory Professor and HHMI-GBMF Investigator Rob Martienssen. In a landmark study that was hailed as one of the breakthroughs of the year by Science magazine in 2002, Martienssen and his colleagues showed that the inheritance of heterochromatin depends on a set of mechanisms broadly defined as RNA interference (RNAi).
In a new study that appears online in Nature on October 16, Martienssen's team, including investigators from the Pasteur Institut in Paris and the University of Salamanca in Spain, describes a new role for RNAi, one that allows the DNA replication process itself to progress smoothly without resulting in DNA damage.
DNA is normally coiled around proteins called histones, which when chemically modified at specific locations, aggregate into dense arrays to form heterochromatin. Martienssen and others had previously found that RNAi guides this histone modification process, which occurs at the same time in the cell cycle when DNA is being duplicated.
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RNAi promotes heterochromatic silencing through replication-coupled release of RNA Pol II
Mikel Zaratiegui et al
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Nature (2011) doi:10.1038/nature10501
Received 20 January 2011 Accepted 25 August 2011 Published online 16 October 2011
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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