Chaperone enzyme provides new target for cancer treatments

Jan 18, 2011

UNC scientists who study how cells repair damage from environmental factors like sunlight and cigarette smoke have discovered how a "chaperone" enzyme plays a key role in cells' ability to tolerate the DNA damage that leads to cancer and other diseases.

The enzyme, known as Rad18, detects a protein called DNA polymerase eta (Pol eta) and accompanies it to the sites of sunlight-induced DNA damage, enabling accurate repair. When Pol eta is not present, alternative error-prone polymerases take its place – a process that leads to DNA mutations often found in cancer cells.

In one known example, faulty DNA repair due to Pol eta- deficiency is responsible for the genetic disease xeroderma pigmentosum-variant, which makes patients extremely susceptible to skin cancers caused by exposure to sunlight. However, scientists did not know how the cells selected the correct DNA Polymerase for error-free repair of each type of DNA damage.

"We found that the mechanism that promotes the 'chaperone' enzyme to recruit Pol eta to sites of is managed by another signaling termed 'Cdc7' which we know is essential to normal regulation of the cellular lifecycle," said lead author Cyrus Vaziri, PhD, who is an associate professor of pathology and laboratory medicine and member of UNC Lineberger Comprehensive Cancer Center. Thus cells employ Cdc7 to ensure accurate DNA repair during the stage of their lifecycle that is most vulnerable to cancer-causing mutations.

The study was published in November in the Journal of Cell Biology.

According to Vaziri, the dual role that Cdc7 plays in the cell lifecycle and DNA repair offers a promising target for potential cancer therapies.

"We know that cancer have high levels of Cdc7 activity and can evade some DNA-damaging therapies such as cis-Platinum through Rad18 and Pol eta activity. We may be able to target this pathway in platinum-resistant tumors to prevent DNA repair and enhance cell killing by platinating agents," he said.

Explore further: Top Japan lab dismisses ground-breaking stem cell study

Related Stories

Recommended for you

Top Japan lab dismisses ground-breaking stem cell study

22 hours ago

Japan's top research institute on Friday hammered the final nail in the coffin of what was once billed as a ground-breaking stem cell study, dismissing it as flawed and saying the work could have been fabricated.

Research sheds light on what causes cells to divide

Dec 24, 2014

When a rapidly-growing cell divides into two smaller cells, what triggers the split? Is it the size the growing cell eventually reaches? Or is the real trigger the time period over which the cell keeps growing ...

Locking mechanism found for 'scissors' that cut DNA

Dec 24, 2014

Researchers at Johns Hopkins have discovered what keeps an enzyme from becoming overzealous in its clipping of DNA. Since controlled clipping is required for the production of specialized immune system proteins, ...

Scrapie could breach the species barrier

Dec 24, 2014

INRA scientists have shown for the first time that the pathogens responsible for scrapie in small ruminants (prions) have the potential to convert the human prion protein from a healthy state to a pathological ...

Extracting bioactive compounds from marine microalgae

Dec 24, 2014

Microalgae can produce high value health compounds like omega-3s , traditionally sourced from fish. With declining fish stocks, an alternative source is imperative. Published in the Pertanika Journal of Tr ...

User comments : 0

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.