Melike Caglayan, Ph.D.
Research: Oxidative Stress, Genome Maintenance, DNA Repair, Nucleic Acids Enzymology
Ph.D from Bogazici University, Istanbul, Turkey, 2010
Office: ARB R3-226A
Dr. Caglayan’s Ph.D. work focused on investigating the temperature effect on the fidelity of bacterial DNA replication and DNA polymerase transient state kinetics. In 2013, she joined the laboratory of Dr. Samuel H. Wilson at National Institutes of Health (NIH), National Institutes of Environmental Health (NIEHS), to study the base excision DNA repair by characterizing nucleic acid-protein and protein-protein interactions and their role in coordinating the sequential enzymatic steps of the DNA repair pathway. Dr. Caglayan joined the faculty at the University of Florida in June 2018.
In living cells, reactive oxygen and nitrogen species are formed continuously as a consequence of metabolic reactions, as well as arising from exposure to environmental agents. The basis of multiple human afflictions such as cancer is rooted in oxidative stress. The oxidative DNA damage (8-oxoG) and oxidized nucleotide pool (8-oxodGTP) are both the most abundant and common threat to genome stability. Base Excision Repair (BER) is responsible for repairing of these cytotoxic and mutagenic DNA base lesions that can lead to genomic instability and cell death. BER is a sequential process that includes channeling of DNA repair intermediates from the gap filling DNA synthesis step by DNA polymerase β to the ligation step by DNA ligase (Scheme, top panel). This hand off protects cells against accumulation of toxic DNA intermediates. DNA ligation, indeed, is a terminal step of almost all types of DNA repair pathways, including base excision repair, mismatch repair, and double-strand break repair.
The precise mechanism as to how unrepaired single-strand break intermediates are generated during the DNA repair pathways is unknown. The overall goal of the lab is to better understand the biological importance and molecular mechanism of the sequential flow of DNA intermediates through the DNA repair pathways under oxidative stress cellular conditions.