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Study reveals new role for RNA interference during chromosomal replication
Date:10/16/2011

tion" spots on the DNA where DNA-building proteins can bind, unzip the double-stranded DNA molecule to create a replication "fork," and begin to build a new strand of it.

This alternate arrangement of regions to be transcribed for heterochromatin assembly and regions that serve as origins for DNA replication raised a new question: how do the transcription machinery and the replication machinery work in tandem without colliding with each other and as a result stall the replication fork and trigger DNA damage?

In a recent study, Martienssen collaborated with scientists at the University of California at Berkeley and showed that the DNA-building proteins themselves could latch on to histone-modifying proteins and pull them along the replication fork.

"This finding raised the question of what role RNAi actually plays during the replication phase of the cell cycle," says Martienssen. "The answers to both questions turned out to be very simple and elegant."

His group's experiments in fission yeast, a simple model system used for studying heterochromatin, show that when the polymerase II enzyme has transcribed a stretch of DNA into RNA, the RNAi mechanism causes the enzyme to release its hold on the DNA and fall away. This allows the replication fork to progress smoothly and the DNA strands to be copied by the replication machinery. The histone-modifying proteins, which follow right along, establish heterochromatin.

The scientists found that failure or absence of the RNAi mechanism stalls replication, which triggers a strong "DNA damage" alert within the cell. That's when a repair mechanism called homologous recombination kicks in and repairs the stalled fork, but the ability to modify histones is lost.

"These experiments have revealed the real role of RNAi during the cell's replication phase, which is to protect cells from this sort of replication-associated fork damage," according to Martienssen.


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Contact: Hema Bashyam
bashyam@cshl.edu
516-367-6822
Cold Spring Harbor Laboratory
Source:Eurekalert

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