The Department of Biochemistry's weekly BCH 252 seminar series is presented this week by

Dr. Alan Tomkinson, Professor, Department of Internal Medicine, Associate Director for Basic Research, Cancer Center- Cellular and Molecular Oncology, University of New Mexico

Seminar Title: "DNA ligase complexes in replication and repair"

Abstract: DNA joining events are required to complete DNA replication, genetic recombination and almost all DNA repair pathways. In human cells, there are three genes LIG1, LIG3, and LIG4, that encode DNA ligases. Each of the ATP-dependent DNA ligase polypeptides encoded by the human LIG genes share a related catalytic region that recognizes and encircles nicked DNA. A major goal of the Tomkinson laboratory has been to determine the cellular functions of these enzymes by complementary genetic and biochemical approaches. These studies have shown that specific protein-protein interactions involving regions adjacent to the catalytic region dictate the cellular functions of the DNA ligases.
Using the atomic resolution structure of human DNA ligase I complexed with nicked DNA, the Tomkinson laboratory identified small molecule inhibitors of human DNA ligases by molecular modelling followed by biochemical and cell-based screening. These inhibitors have been utilized as probes of DNA ligase function in normal and cancer cells, leading to the identification of an abnormality in the repair of DNA double strand breaks (DSB)s in cancer cell lines and samples from cancer patients. Recent studies in which the processing and joining of DNA strand breaks have been reconstituted and the multiprotein complexes formed by DNA ligases characterized by biophysical approaches will be described.

Faculty Host: Dr. Jeff Perry, jeff.perry@ucr.edu