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

Cold Spring Harbor, N.Y. 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 withinwhich could wreck the genome if activatedas 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 inheritanceinformation not transmitted through the DNA code itself but by the way in which it is packagedhas 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.

In this RNAi-guided process, an enzyme called polymerase II copies or "transcribes" specific regions of DNA into RNA molecules, and somehow this modifies histones in those exact regions, thereby creating heterochromatin. These heterochromatic regions, however, alternate with so-called "origins of replication" 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.


'/>"/>

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

Related biology news :

1. Method of studying roots rarely used in wetlands improves ecosystem research
2. Southampton scientists herald significant breakthrough in study of chlamydia
3. Einstein College of Medicine given $6.7 million to study congenital heart defect genetics
4. National Science Foundation selects University of Colorado Denver team to study city sustainability
5. Worms among first animals to surface after K-T extinction event, CU-led study finds
6. Researchers study agings effect on the brain
7. Cleveland Clinic study discovers new targets for treating inflammatory, autoimmune diseases
8. Gray jays winter survival depends on food storage, study shows
9. Study tracks mutations causing CDA II back to the Roman Empire
10. New data-mining effort launched to study mental disorders
11. Study suggests childrens food choices are affected by direct advertising and parental influence
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/20/2016)... May 20, 2016  VoiceIt is excited to ... VoicePass. By working together, VoiceIt and ... VoiceIt and VoicePass take slightly different approaches to ... both security and usability. ... this new partnership. "This marketing and ...
(Date:5/3/2016)... 3, 2016  Neurotechnology, a provider of high-precision ... Automated Biometric Identification System (ABIS) , a complete ... MegaMatcher ABIS can process multiple complex biometric transactions ... of fingerprint, face or iris biometrics. It leverages ... and MegaMatcher Accelerator , which have been ...
(Date:4/26/2016)... -- Research and Markets has announced the ...  report to their offering.  , ,     (Logo: ... forecast the global multimodal biometrics market to grow ... 2016-2020.  Multimodal biometrics is being implemented ... healthcare, BFSI, transportation, automotive, and government for controlling ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... 2016  Liquid Biotech USA ... a Sponsored Research Agreement with The University of ... from cancer patients.  The funding will be used ... with clinical outcomes in cancer patients undergoing a ... be employed to support the design of a ...
(Date:6/24/2016)... ... , ... Researchers at the Universita Politecnica delle Marche in Ancona combed medical ... mesothelioma. Their findings are the subject of a new article on the Surviving Mesothelioma ... in the blood, lung fluid or tissue of mesothelioma patients that can help point ...
(Date:6/23/2016)... A person commits a crime, and the detective ... the criminal down. An outbreak of foodborne illness ... (FDA) uses DNA evidence to track down the bacteria that ... It,s not. The FDA has increasingly used a complex, cutting-edge ... illnesses. Put as simply as possible, whole genome sequencing is ...
(Date:6/23/2016)... June 23, 2016   EpiBiome , a precision ... million in debt financing from Silicon Valley Bank (SVB). ... and to advance its drug development efforts, as well ... "SVB has been an incredible strategic partner ... a traditional bank would provide," said Dr. Aeron ...
Breaking Biology Technology: