New Hope for Anti-Cancer Drugs After UCSD Discoveries on DNA Lesions

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Ultraviolet radiation, such as sunlight, can damage cellular DNA, leading to cancer. UC San Diego researchers have described the underlying mechanism that helps explain why such damage isn’t always repaired. Images via Dong Wang, UC San Diego.

Researchers at the UC San Diego School of Medicine Wednesday announced their success in determining that a type of DNA-repairing enzyme is neutralized by DNA lesions caused by exposure to ultraviolet light.

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RNA polymerases are enzymes that monitor, detect and repair damaged sections of DNA to maintain genetic integrity. The researchers found that the processes of a specific polymerase, called Pol 1, stalled when it attempted to repair a lesion caused by UV light damage in a DNA strand.

The upshot of the study is that the findings could possibly lead to the development of novel anti-cancer drugs that harness Pol 1’s transcription ability, according to Dr. Dong Wang, the study’s co-corresponding author and an associate professor at UCSD.

Pol 1 is responsible for up to 60 percent of transcription activity in growing cells, and for identifying lesions and activating repairs at the site of the lesion, according to the study. If left unchecked, DNA lesions caused by UV light exposure can result in cancerous growths such as melanoma.

“[Pol 1 is] the most active RNA polymerase in growing cells and so its ability to identify lesions has significant influence on whether a cell can survive UV-caused genetic damage,” Wang said. “However, little is known about how this enzyme actually processes UV-induced lesions.”

The study, published this week in the journal PNAS, was a collaborative effort with researchers in Spain and Finland. Funding came from the National Institutes of Health, the Spanish Ministry of Science and the Ramon Areces Foundation.

— City News Service

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