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 stalled 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. Previously, the human Y-family DNA pol kappa (Polk) has been determined to perform translesion DNA synthesis across DNA that has been damaged with the lung carcinogen, 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. Currently, we are performing structure function experiments to determine what specific architectural components within pol kappa's structure are important for lesion bypass. We will present the role of the novel N-clasp domain and its importance in bypass of benzo[a]pyrene modified DNA.

Role of the N-clasp domain of human DNA polymerase kappa

247th National Meeting (2014)

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