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Researchers identify key enzyme in DNA repair pathway

WASHINGTON, July 30 — Researchers have discovered an enzyme crucial to a type of DNA repair that also causes resistance to a class of cancer drugs most commonly used against ovarian cancer.

Scientists from the University of Texas MD Anderson Cancer Center in the United States and the Life Sciences Institute of Zhejiang University in China reported on Thursday the discovery of the enzyme and its role in repairing DNA damage called cross- linking in the Science Express advance online publication of Science.

The enzyme, which they named FAN1, appears to be a nuclease, which is capable of slicing through strands of DNA.

In a series of experiments, researchers demonstrated how the protein complex summons FAN1, connects with the enzyme and moves it to the site of DNA cross-linking. They also showed that FAN1 cleaves branched DNA but leaves the normal, separate double- stranded DNA alone. Mutant versions of FAN1 were unable to slice branched DNA.

The researchers also demonstrated that FAN1 cannot get at DNA damage without being taken there by the FANCI-FANCD2 protein complex, which detects and moves to the damaged site. The complex recruits the FAN1 enzyme by acquiring a single ubiquitin molecule. FAN1 connects with the complex by binding to the ubiquitin site.

Analyzing the activity of this repair pathway could guide treatment for cancer patients, researchers said, with the platinum- based therapies used when the cross-linking repair mechanism is less active. (PNA/Xinhua)


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