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Cancer bound
Date:11/2/2012

A person doesn't have to go far to find a polycyclic aromatic hydrocarbon (PAH). These carcinogen precursors are inhaled through automobiles exhaust during the morning commute, are present in a drag of cigarette smoke, and are part of any barbequed meal.

Once ingested or inhaled, these big, bulky multi-ringed molecules are converted into reactive carcinogenic compounds that can bind to DNA, sometimes literally bending the double helix out of its normal shape, to form areas of damage called lesions. The damaged DNA can create errors in the genetic code during replication, which may cause cancer-initiating mutations.

It is the job of the nuclear excision repair (NER) system to repair damage caused by PAH lesions by removing the segment of DNA where the lesion is bound and patching up the resulting gap. But some lesions are especially resistant to this repair machinery, making them much more likely to cause mutations than lesions that are promptly repaired.

A research team at New York University (NYU) has gained new insight on the ability of certain PAH-derived lesions to evade the DNA repair machinery. They found that some lesions stabilize the DNA they damage, making it difficult for a certain repair protein to mark the lesion for repair. Their research was published earlier this year in the February 2012 issue of Biochemistry. More recent articles about NER of DNA lesions from the same group appeared in Nucleic Acids Research in July and August.

"Some lesions cause DNA to be locally destabilized, but there are lesions that actually stabilize the DNA so that the two strands come apart with great difficulty," said Suse Broyde, a biology professor at NYU. "Sometimes they're even more stable than undamaged DNA."

The stability of the DNA double helix is a key feature that determines whether DNA is flagged for repair in the first place by a protein called XPC. The protein patrols the genome looking for weakened are
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Contact: Aaron Dubrow
aarondubrow@tacc.utexas.edu
512-475-9439
University of Texas at Austin, Texas Advanced Computing Center
Source:Eurekalert  

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