Department of Biochemistry and Molecular Biology

Biography:
Recipient of:  National Institutes of Health Career Development Award; Distinguished Faculty Research Award from the Graduate School of Biomedical Sciences, University of Texas Medical Branch in 2004; Environmental Mutagen Society Award for Many Years of Outstanding Research into the Mechanics of DNA Repair and Mutagenesis in Eukaryotic Cells in 2005.
Elected Fellow of the American Association for the Advancement of Science in 2005, and Fellow of the American Academy of Microbiology  in 2009.

Research Interests:
The long-term objective of the L. Prakash laboratory is to understand the means eukaryotic cells employ to replicate damaged DNA templates. A detailed understanding of the mechanisms by which human cells manage to replicate through a diverse variety of DNA lesions generated by cellular reactions and by external environmental agents is important because defects in DNA repair and related processes that promote replication of damaged DNA cause genome instability and lead to carcinogenesis. The Prakash laboratory has been a pioneer in DNA repair studies in eukaryotes.

Roles of human translesion synthesis DNA polymerases: Translesion synthesis (TLS) DNA polymerases (Pols) are uniquely adapted to replicate through different types of DNA lesions.  A large number of TLS Pols have been identified in humans since the discovery and elucidation of the role of Pol eta in TLS in the Prakash research group.  As determined from a combination of genetic, biochemical, and structural studies, Pol eta can replicate through the UV induced covalently linked cyclobutane pyrimidine dimer because of its unique ability to accommodate two template residues in its active site.  Another DNA polymerase, Pol iota, pushes the purine template residue A or G into a syn conformation and forms a Hoogsteen base pair with the incoming nucleotide.  This allows Pol iota a specific ability to replicate through DNA adducts which impair normal Watson-Crick base pairing.  Rev1 is a highly specialized polymerase for incorporating nucleotides opposite N2-dG minor groove DNA adducts.  Studies carried out by this group have also shown that divergence and specialization occurs in the roles of other TLS Pols; moreover, whereas some TLS Pols are specialized for inserting a nucleotide opposite the DNA lesion, others carry out the subsequent extension of synthesis from the nucleotide opposite from the DNA lesion.  Ongoing studies in the Prakash group are analyzing the mechanisms that underlie the unusually high fidelity with which TLS Pols replicate through DNA lesions, determining the mechanisms that control placement of TLS machinery in conjunction with the replication fork stalled at DNA lesions, and delineating the consequences of impairment of any aspects of the TLS process.