DNA carcinogens have the potential to chemically modify DNA and, in turn, potentially alter the DNA's coding potential.  Normal DNA replication machinery is severely retarded when a DNA lesion is encountered.  Recently, a new class of DNA polymerases, termed translesion or bypass polymerases, has been shown to perform DNA synthesis across DNA that has been damaged by chemical modifications.  The environmental mutagen and carcinogen, benzo[a]pyrene, has been reported to be one of the major carcinogens found in cigarette smoke. Previously, the Y-family DNA Polk has been determined to perform translesion DNA synthesis across DNA that has been damaged with benzo[a]pyrene.  However, little information is known about the mechanism by which Polk is able to perform DNA synthesis through this lesion.  The novel domain of Polk, termed the N-clasp, has been shown to be essential for this polymerase's ability to replicate undamaged DNA.  In order to gain a deeper understanding of the N-clasp domain of Polk's, we plan to create several amino acid changes in the N-clasp domain and then examine how these changes affect the ability to perform DNA synthesis across from benzo[a]pyrene damaged DNA.

Structural based mutagenesis analysis of DNA polymerase kappa N-clasp domain

243rd National Meeting (2012)

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