Lata Balakrishnan, Ph.D.
Associate Professor
Director of Graduate Studies
Biology
Associate Professor
Director of Graduate Studies
Biology
The current research in our laboratory is focused on understanding the mechanistic reactions of eukaryotic lagging strand DNA synthesis, and the accompanying DNA repair processes. We have recently acquired evidence that many of the protein players in lagging strand DNA synthesis and base excision repair are post-translationally modified by lysine acetylation. Accurate DNA replication and repair is a means by which eukaryotic cells maintain the integrity of their genomes.
Understanding these processes is important because the errors that build up over decades in humans are a direct cause of aging and disease. Studies of DNA replication and repair carried out so far, have focused on understanding the pathways and on identifying targets for cancer radiation, chemotherapeutic drugs, and anti-viral drugs. Interestingly, recent cancer therapies have centered on the use of deacetylase inhibitors, which elevate levels of acetylation of nuclear DNA repair, heat shock and signaling proteins.
However, we have virtually no understanding of how acetylation alters the enzymatic functions of these proteins, in turn, regulating DNA synthesis fidelity and repair. Through our research, we are proposing to extend the scope of our current work beyond characterizing basic mechanistic pathways, to understanding how the proteins are fine-tuned by post-translational modifications to ensure best error-free replication and repair, altering mutagenesis rates.
In particular, based on evidence from several laboratories including our current work, we propose protein lysine acetylation as a general method employed by cells to regulate the fidelity of DNA replication and repair. In our laboratory, we will be combining three powerful tools; biochemistry, chromatin biology and genetics to understand this regulatory process.