Stopgap DNA repair needs a second step

May 04, 2009

One can have a dream, two can make that dream so real, goes a popular song. Now a Weizmann Institute study has revealed that it takes two to perform an essential form of DNA repair.

Prof. Zvi Livneh of the Weizmann Institute's Department has been studying for some two decades: 'Considering that the DNA of each cell is damaged about 20,000 times a day by radiation, pollutants and harmful chemicals produced within the body, it's obvious that without effective DNA repair, life as we know it could not exist. Most types of damage result in individual mutations - genetic 'spelling mistakes' - that are corrected by precise, error-free .

Sometimes, however, damage results in more than a mere spelling mistake; it can cause gaps in the DNA, which prevent the DNA molecule from being copied when the cell divides, much like an ink blot or a hole on a book page interferes with reading. So dangerous are these gaps that the cell resorts to a sloppy but efficient repair technique to avoid them: It fills in the missing DNA in an inaccurate fashion. Such repair can save the cell from dying, but it comes at a price: this error-prone mechanism, discovered at the Weizmann Institute and elsewhere about a decade ago, is a major source of mutations.'

In a recent study he conducted with graduate students Sigal Shachar and Omer Ziv, as well as researchers from the US and Germany, Livneh revealed how the error-prone repair works. The team found that such repair proceeds in two steps and requires two types of enzymes, belonging to the family of enzymes called DNA polymerases, which synthesize DNA. First, one repair enzyme, 'the inserter,' does its best to fit in a genetic 'letter' into the gap, opposite the damaged site in the DNA molecule; several enzymes can perform this initial step, which often results in the insertion of an incorrect genetic letter. Next, another enzyme, 'the extender,' helps to restore regular copying of DNA by attaching additional DNA letters after the damaged site; only one repair enzyme is capable of performing this vital second step. These findings were published recently in the EMBO Journal.

Understanding how this major form of DNA repair works can have significant clinical implications. Since defects in this process increase the risk of cancer, clarifying its nuts and bolts might one day make it possible to enhance it in people whose natural DNA repair is deficient. In addition, manipulating this mechanism can improve the effectiveness of cancer drugs. Cancer cells can resist chemotherapy by exploiting their natural repair mechanisms, and blocking these mechanisms may help overcome this resistance, leading to a targeted destruction of the cancerous tumor.

More information: www.nature.com/emboj/journal/v… l/emboj2008281a.html

Source: Weizmann Institute of Science (news : web)

Explore further: Conjecture on the lateral growth of Type I collagen fibrils

add to favorites email to friend print save as pdf

Related Stories

Real-time observation of the DNA-repair mechanism

May 22, 2008

For the first time, researchers at Delft University of Technology have witnessed the spontaneous repair of damage to DNA molecules in real time. They observed this at the level of a single DNA molecule. Insight into this ...

DNA repair mechanisms relocate in response to stress

Mar 26, 2009

Like doctors making house calls, some DNA repair enzymes can relocate to the part of the cell that needs their help, a collaborative team of scientists at Emory University School of Medicine has found.

Chromosome glue repairs damaged DNA

Jul 13, 2007

When a strand of DNA breaks in the body's cells, it normally does not take long until it has been repaired. Now researchers at the Swedish medical university Karolinska Institutet have discovered a new mechanism that helps ...

New understanding of DNA repair

Feb 16, 2006

A mechanism by which genes are repaired has been described in detail for the first time. This new understanding may, in the long term, provide the scientific foundation upon which therapies to treat genetic diseases or cancers ...

Study: Cells prevent DNA repair

Nov 23, 2005

Scientists say they've discovered cells co-opt the machinery that usually repairs broken strands of DNA to protect the integrity of chromosomes.

Recommended for you

Chemical biologists find new halogenation enzyme

7 hours ago

Molecules containing carbon-halogen bonds are produced naturally across all kingdoms of life and constitute a large family of natural products with a broad range of biological activities. The presence of halogen substituents ...

Protein secrets of Ebola virus

12 hours ago

The current Ebola virus outbreak in West Africa, which has claimed more than 2000 lives, has highlighted the need for a deeper understanding of the molecular biology of the virus that could be critical in ...

Protein courtship revealed through chemist's lens

12 hours ago

Staying clear of diseases requires that the proteins in our cells cooperate with one another. But, it has been a well-guarded secret how tens of thousands of different proteins find the correct dancing partners ...

Decoding 'sweet codes' that determine protein fates

14 hours ago

We often experience difficulties in identifying the accurate shape of dynamic and fluctuating objects. This is especially the case in the nanoscale world of biomolecules. The research group lead by Professor Koichi Kato of ...

Conjecture on the lateral growth of Type I collagen fibrils

Sep 12, 2014

Whatever the origin and condition of extraction of type I collagen fibrils, in vitro as well as in vivo, the radii of their circular circular cross sections stay distributed in a range going from 50 to 100 nm for the most ...

User comments : 0