DNA mismatch repair happens only during a brief window of opportunity

December 22, 2011

In eukaryotes – the group of organisms that include humans – a key to survival is the ability of certain proteins to quickly and accurately repair genetic errors that occur when DNA is replicated to make new cells.

In a paper published in the December 23, 2011 issue of the journal Science, researchers at the Ludwig Institute for Cancer Research and the University of California, San Diego School of Medicine have solved part of the mystery of how these proteins do their job, a process called repair (MMR).

"One of the major questions in MMR is how MMR proteins figure out which base in a mispair is the wrong one," said Ludwig Institute assistant investigator Christopher D. Putnam, PhD, an adjunct assistant professor of medicine at UC San Diego. "For example, if (G) is inappropriately in a base-pair with (T), is the G or the T the error? Picking the wrong base results in mutations, not fixes."

Using Saccharomyces cerevisiae, or baker's yeast, as their model organism, the researchers, led by Richard D. Kolodner, PhD, Ludwig Institute investigator and UCSD professor of medicine and cellular and molecular medicine, discovered that newly replicated DNA produces a temporary signal for 10 to 15 minutes after replication which helps identify it as new – and thus a potential subject for MMR.

The actual signal was not identified, but Putnam said it might be tell-tale nicks in single-stranded DNA or certain proteins associated with replication. The scientists are working to pinpoint the precise signal.

The findings, combined with earlier, published work that visualized MMR in a living cell for the first time, more fully explains how eukaryotes eliminate DNA replication errors, which can result in defects and the development of cancers.

"How eukaryotes identify the newly synthesized strand of DNA is a mystery that has persisted for at least 30 years," said Putnam. "These findings really change our ideas of how MMR works," said Putnam.

Explore further: Researchers uncover potential mechanisms to protect against genetic alterations, diseases

Related Stories

Study finds smoking related to subset of colorectal cancers

April 14, 2008

Smoking puts older women at significant risk for loss of DNA repair proteins that are critical for defending against development of some colorectal cancers, according to research from a team led by Mayo Clinic scientists.

Scientists identify molecular basis for DNA breakage

July 19, 2011

Scientists from the Hebrew University have identified the molecular basis for DNA breakage, a hallmark of cancer cells. The findings of this research have just been published in the journal Molecular Cell.

Recommended for you

New approach improves potential HIV vaccine

March 29, 2017

By engineering an on/off switch into a weakened form of HIV, University of Nebraska-Lincoln researchers have enhanced the safety and effectiveness of a potential vaccine for the virus that has killed approximately 35 million ...

How non-muscle cells find the strength to move

March 29, 2017

Researchers from the Mechanobiology Institute, Singapore (MBI) at the National University of Singapore have described, for the first time, the ordered arrangement of myosin-II filaments in actin cables of non-muscle cells. ...

Cats found to like humans more than thought

March 29, 2017

(Phys.org)—A trio of researchers with Oregon State University and Monmouth University has conducted experiments with cats, and has found that they appear to like humans more than expected. In their paper published in the ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.