Biochemistry and Molecular Biology

University of Texas Medical Branch


Faculty

Satya Prakash, Ph.D., Professor

The S. Prakash laboratory concentrates on the study of DNA repair processes in the yeast Saccharomyces cerevisiae and in humans.The goals are to define the roles of the various protein components involved in nucleotide excision repair and base excision repair, and to study the interconnections of these repair processes with transcription, replication, and cell cycle.In addition, the mechanisms which promote transcription and replication through DNA lesions are being studied.The Prakash laboratory has been a pioneer in DNA repair studies, and he and his colleagues have elevated yeast to a position as the primary medium for research in DNA repair in eukaryotes.

DNA Repair in Yeast and Humans :Studies stemming from the Prakash laboratory have been instrumental in identifying the key protein factors required for nucleotide excision repair in eukaryotes, and in defining their roles in different stages of the repair reaction.The Prakash group has reconstituted the incision step of nucleotide excision repair with highly purified yeast proteins, and this system is being used to examine the mechanisms of damage recognition, and to determine the roles of different SWI/SNF protein factors involved in the initial step of damage recognition in chromatin remodeling.Such a coupling of damage recognition and chromatin remodeling within a protein complex would provide for highly efficient repair of non-transcribed regions of the genome.

Transcriptional Bypass of DNA Lesions: This project examines the mechanisms by which eukaryotic cells overcome blocks to RNA polymerase II (Pol II) transcription conferred by the presence of DNA lesions in the template strand.Cockayne syndrome (CS) in humans is characterized by severe growth and mental retardation, and mutations in the CSA, CSB, XPG, XPB, and XPD genes can cause CS.The Prakash group has utilized the yeast system to demonstrate the involvement of the RAD26 and RAD2 genes, the yeast counterparts of the human CSB and XPG genes, respectively, in Pol II transcription in undamaged cells and in promoting Pol II transcription through damaged bases and abasic sites.These studies have implicated a role for the various human CS protein factors in transcription elongation on undamaged and damaged DNAs.

Replication of Damaged DNA:The manner by which eukaryotic cells replicate through DNA lesions is being studied in S. cerevisiae and humans.DNA polymerase eta, discovered in the Prakash laboratory, has the unique ability to proficiently replicate through UV induced cyclobutane pyrimidine dimers and through a variety of other DNA lesions.The roles of this DNA polymerase and of many other yeast (Pol zeta, Rev1) and human translesion synthesis polymerases (Pol eta, Pol iota, and Pol kappa) in the replication of damaged DNA are being studied, and biochemical and structural studies are ongoing to understand the action mechanism of these polymerases in lesion bypass.