[ RadSafe ] DNA Mismatch Repair Happens Only During A Brief Window of Opportunity

[ROY HERREN]

http://ucsdnews.ucsd.edu/pressreleases/dna_mismatch_repair_happens_only_during_a_brief_window_of_opportunity/

December 22, 2011 | By Scott LaFee 


DNA Mismatch Repair Happens Only During A Brief Window of Opportunity
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 DNA mismatch repair (MMR).
“One of the major questions in MMR is how MMR proteins figure out which base in 
a DNA 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 guanine (G) is inappropriately in a base-pair with 
thymine (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.
Co-authors include Hans Hombauer and Anjana Srivatsan of the Ludwig Institute 
for Cancer Research, UCSD Departments of Medicine and Cellular and Molecular 
Medicine, Institute of Genomic Medicine and UC San Diego Moores Cancer Center.
Funding for this research came from the National Institutes of Health.
Media Contact
Scott LaFee, 619-543-6163, slafee at ucsd.edu