Sankar Mitra, Ph.D., Professor
The broad research theme in the Mitra Laboratory is repair of oxidative damage in mammalian genomes and its signaling and regulation. The Mitra lab uses a comprehensive approach by utilizing a variety of tools ranging from enzymology, molecular/cellular biology to structural biology (in collaborative efforts) and transgenic mouse studies to address basic issues about mutagenesis/carcinogenesis, and aging caused by reactive oxygen species (ROS), which react with most cellular macromolecules, and are continuously generated during respiration. These are also induced exogenously due to inflammation, infection and anti-tumor drug treatment. Even though a variety of cellular processes have evolved to counter ROS, oxidative stress is required for many cellular signaling processes to maintain homeostasis. ROS are genotoxic, and generate a wide variety of mutagenic and toxic lesions in both nuclear and mitochondrial genomes, which are repaired primarily via the base excision repair (BER) pathway.
Current research efforts in the Mitra Lab are focused on two topics, namely, (1) role of NEILs in repair of oxidatively damaged bases, and (2) distinct functions of APE1, a central player in base damage and single strand break repair with additional novel functions in transcription regulation.
Ongoing Research Projects:
- Characterization of complexities in base excision repair (BER) processes, e.g., replication-associated repair of oxidized bases.
- Testing the hypothesis that APE in mitochondria is more critical for cell survival.
- Exploring how altered APE1 level affects aging and mortality in transgenic mice.
- Molecular basis for APE1’s transcriptional functions.
Recent key findings made in the Mitra Laboratory are:
- Covalent modification (acetylation) of DNA glycosylases and APE1 and their implications in genome repair and gene regulation.
- Discovery and characterization of the NEIL family of DNA glycosylases and their specialized functions in BER; consequential discovery of an APE-independent BER subpathway.
- Essentiality of repair and gene regulatory functions of APE1.
- Identification of mitochondrial APE as a truncation product of nuclear APE1.