Stopgap DNA repair needs a second step

May 4, 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: Real-time observation of the DNA-repair mechanism

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

March 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

July 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

February 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

November 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

Artificial photosynthesis gets big boost from new catalyst

November 20, 2017

A new catalyst created by U of T Engineering researchers brings them one step closer to artificial photosynthesis—a system that, just like plants, would use renewable energy to convert carbon dioxide (CO2) into stored chemical ...

Scientific advances can make it easier to recycle plastics

November 17, 2017

Most of the 150 million tons of plastics produced around the world every year end up in landfills, the oceans and elsewhere. Less than 9 percent of plastics are recycled in the United States, rising to about 30 percent in ...

The spliceosome—now available in high definition

November 17, 2017

UCLA researchers have solved the high-resolution structure of a massive cellular machine, the spliceosome, filling the last major gap in our understanding of the RNA splicing process that was previously unclear.

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.