Dr. Sukesh Bhaumik’s Lab
Dr. Sukesh R. Bhaumik
B. Sc. Ramakrishna Mission Residential College, Narendrapur (University of Calcutta),1990; M. Sc. Indian Institute of Technology, Bombay, 1992; Ph. D. Tata Institute of Fundamental Research, Bombay, 1997; Postdoctoral Fellow, Howard Hughes Medical Institute at the University of Massachusetts Medical School, 1998-2003; Appointed as faculty, Dept. of Biochemistry & Molecular Biology, SIUC, 2003-present.
Chromatin Structure, Transcription and Transcription-coupled DNA Repair
Our laboratory has a broad research interest in understanding the regulatory mechanisms of eukaryotic transcription and transcription-coupled DNA repair, using a variety of experimental approaches that involve molecular biological, biophysical, biochemical and genetic methodologies. With this view, we have primarily focused our research on the following three projects. We are also studying chromatin structure and its role in regulation of gene expression and DNA repair.
A. Understanding the mechanisms of eukaryotic transcription-coupled ubiquitination and DNA repair in vivo. Genome integrity is continuously threatened by the occurrence of DNA damage arising from cellular metabolism or following genotoxic attack. An accumulation of genetic damage and the ensuing uncontrolled cell proliferation is the major cause of cancer and other genetic diseases. A major threat to cellular viability is posed by DNA damage that blocks transcription. A preferential repair process that rapidly removes lesions from the transcribed strands of the active genes, known as transcription-coupled DNA repair (TCR), is an essential cellular defense mechanism. TCR occurs in both prokaryotes and eukaryotes. The mechanism of TCR is complex in eukaryotes, and it is generally thought that a stalled RNA polymerase can ultimately resume transcript synthesis following DNA repair. However, the recent finding that Rpb1 which is the largest subunit of RNA polymerase II, is ubiquitinated and then degraded in response to DNA damage, suggests an alternative mechanism for down-regulation of transcription. The precise in vivo mechanism of ubiquitination of Rpb1 and its role in DNA repair remains unknown. We have focused our research to determine the cellular mechanisms that couple transcription to genome integrity in living eukaryotic cells in response to DNA damage, using a variety of experimental approaches that include ChIP, FRET, genetic, cell and molecular biology. The outcomes of this research will enhance our understanding of the mechanisms of TCR. Such a knowledge will have highly significant impact in public health, since a growing number of cancer and other human diseases are related to TCR.
B. Understanding the regulatory mechanisms of eukaryotic gene expression by the proteasome complex in vivo. The 26S proteasome complex is engaged in an ATP-dependent proteolytic degradation of short-lived as well as long-lived proteins, processing of some proteins, and antigen presentation. Recently, the proteasome complex has been implicated in regulation of transcription at the levels of initiation, elongation and termination. However, the precise mechanisms of gene regulation by the proteasome complex remain largely unknown. Understanding the regulatory mechanisms of gene expression by the proteasome complex is crucial for designing better therapeutic agents to maintain normal functions of cells, since a growing number of human diseases are linked to the proteasome complex. Thus, our long term goal is to understand the mechanisms of eukaryotic gene regulation by the proteasome complex. We are currently carrying out the experiments to determine the mechanism-of-action of the proteasome complex in regulation of eukaryotic transcriptional initiation or activation in vivo. In future, we will extend our study to understand the role of the proteasome complex in coordinating elongation, termination, and RNA processing events at the active gene.
C. Dissecting the mechanisms of eukaryotic transcriptional activation in vivo. Genetic, structural, and biochemical efforts combined with genome-wide expression analysis have advanced our understanding of the mechanisms of eukaryotic transcriptional activation. Despite these advances, our knowledge on how transcriptional activators interact with and regulate components of the transcription machinery in vivo is lacking, primarily because of unavailability of appropriate experimental methods. We have recently demonstrated how elegant approaches such as FRET and ChIP can be used (i) for identification of the physiological targets of the transcriptional activators, and (ii) for delineation of the activator-target stimulated specific protein interaction network at the promoter in vivo. Using these approaches, our long-term research goal is to unravel, at the molecular level, how promoter-specific activators function through a common general machinery to stimulate transcription in vivo.
Teaching Experience (Click Here)
I245 Lincoln Drive,
Neckers Building, Room# 216
Zip Code: 62901
Phone: 618-453-6479 (Office)