Navigation Links
Study identifies mechanisms cells use to remove bits of RNA from DNA strands
Date:12/4/2011

When RNA component units called ribonucleotides become embedded in genomic DNA, which contains the complete genetic data for an organism, they can cause problems for cells. It is known that ribonucleotides in DNA can potentially distort the DNA double helix, resulting in genomic instability and altered DNA metabolism, but not much is known about the fate of these ribonucleotides.

A new study provides a mechanistic explanation of how ribonucleotides embedded in genomic DNA are recognized and removed from cells. Two mechanisms, enzymes called ribonucleases (RNases) H and the DNA mismatch repair system, appear to interplay to root out the RNA components.

"We believe this is the first study to show that cells utilize independent repair pathways to remove mispaired ribonucleotides embedded in chromosomal DNA, which can be sources of genetic modification if not removed," said Francesca Storici, an assistant professor in the School of Biology at the Georgia Institute of Technology. "The results also highlight a novel case of genetic redundancy, where the mismatch repair system and RNase H mechanisms compete with each other to remove misincorporated ribonucleotides and restore DNA integrity."

The findings were reported Dec. 4, 2011 in the advance online publication of the journal Nature Structural & Molecular Biology. The research was supported by the Georgia Cancer Coalition, National Science Foundation and Georgia Tech Integrative BioSystems Institute.

Storici and Georgia Tech biology graduate students Ying Shen and Kyung Duk Koh conducted the study in collaboration with Bernard Weiss, a professor emeritus in the Department of Pathology and Laboratory Medicine at Emory University.

"We wanted to understand how cells of the bacterium Escherichia coli and the yeast Saccharomyces cerevisiae tolerate the presence of different ribonucleotides embedded in their genomic DNA. We found that the structure of a ribonucleotide tract embedded in DNA influenced its ability to cause genetic mutations more than the tract's length," said Storici.

With double-stranded DNA, when wrong bases are paired or one or few nucleotides are in excess or missing on one of the strands, a mismatch is generated. If mismatches are not corrected, they can lead to mutations.

The researchers found that single mismatched ribonucleotides in chromosomal DNA were removed by either the mismatch repair system or RNase H type 2. Mismatched ribonucleotides in the middle of at least four other ribonucleotides required RNase H type 1 for removal.

"We were excited to find that a DNA repair mechanism like mismatch repair was activated by RNA/DNA mismatches and could remove ribonucleotides embedded in chromosomal DNA," explained Storici. "In future studies, we plan to test whether other DNA repair mechanisms, such as nucleotide-excision repair and base-excision repair, can also locate and remove ribonucleotides in DNA."

Using gene correction assays driven by short nucleic acid polymers called oligonucleotides, the researchers showed that when ribonucleotides embedded in DNA were not removed, they served as templates for DNA synthesis and produced a mutation in the DNA. If both the mismatch repair system and RNase H repair mechanisms are disabled, ribonucleotide-driven gene modification increased by a factor of 47 in the yeast and 77,000 in the bacterium.

Defects in the mismatch repair system are known to predispose a person to certain types of cancer. Because the mismatch repair system is conserved from unicellular to multicellular organisms, such as humans, this study's findings open up the possibility that defects in the mismatch repair system could have consequences more critical than previously thought given the newly identified function of mismatch repair to target RNA/DNA mispairs.


'/>"/>
Contact: Abby Robinson
abby@innovate.gatech.edu
404-385-3364
Georgia Institute of Technology Research News
Source:Eurekalert  

Related biology news :

1. Loyola receives NIH grant to study vitamin D deficiency in African populations
2. UI engineers conduct residential soils study, one of few such US studies ever done
3. Skin bones helped large dinosaurs survive, new study says
4. New study to test unusual hypothesis on beta brainwaves
5. UIC study identifies a key molecular switch for telomere extension by telomerase
6. Studying bat skulls, evolutionary biologists discover how species evolve
7. Genetic study confirms: First dogs came from East Asia
8. First study to reveal how paracetamol works could lead to less harmful pain relief medicines
9. New Study Shows Impact of Employee Wellness Efforts
10. New study identifies novel role for PEA-15 protein in cancer growth
11. UT Dallas research widens study of brains role in tinnitus
Post Your Comments:
*Name:
*Comment:
*Email:
Related Image:
Study identifies mechanisms cells use to remove bits of RNA from DNA strands
(Date:6/27/2016)... Research and Markets has announced the addition of the "Biometrics ... The report forecasts the biometrics market ... CAGR of 12.28% during the period 2016-2020. The ... inputs from industry experts. The report covers the market landscape and ... a discussion of the key vendors operating in this market. ...
(Date:6/22/2016)... Md. , June 22, 2016  The American College ... Trade Show Executive Magazine as one of the ... on May 25-27 at the Bellagio in Las ... on the highest percentage of growth in each of the ... of exhibiting companies and number of attendees. The 2015 ACMG ...
(Date:6/22/2016)... June 22, 2016   Acuant , ... verification solutions, has partnered with RightCrowd ® ... for Visitor Management, Self-Service Kiosks and Continuous ... that add functional enhancements to existing physical ... and venues with an automated ID verification ...
Breaking Biology News(10 mins):
(Date:6/27/2016)... GUELPH, ON , June 27, 2016 /PRNewswire/ - BIOREM ... it has been advised by its major shareholders, Clean ... LP, United States based venture ... common shares of Biorem (on a fully diluted, as ... for the disposition of their entire equity holdings in ...
(Date:6/27/2016)... ... June 27, 2016 , ... ... Amgen, will join the faculty of the University of North Carolina Kenan-Flagler ... of strategy and entrepreneurship at UNC Kenan-Flagler, with a focus on the school’s ...
(Date:6/24/2016)... ... , ... While the majority of commercial spectrophotometers and fluorometers use the z-dimension ... are higher end machines that use the more unconventional z-dimension of 20mm. Z-dimension ... bottom of the cuvette holder. , FireflySci has developed several Agilent flow cell ...
(Date:6/23/2016)... /PRNewswire/ - FACIT has announced the creation of ... company, Propellon Therapeutics Inc. ("Propellon" or "the Company"), ... portfolio of first-in-class WDR5 inhibitors for the treatment ... represent an exciting class of therapies, possessing the ... cancer patients. Substantial advances have been achieved with ...
Breaking Biology Technology: