Dr. Rohini Muthuswami

WELCOME TO THE CHROMATIN REMODELING LABORATORY (CRL)

JNU	SLS	CRL	RESEARCH	PEOPLE	COURSES	CONTACT
ATP-dependent chromatin remodelling is essential for DNA replication, repair, transcription, and recombination. The process uses the energy released by hydrolysis of ATP to move nucleosomes across the DNA, making it accessible for proteins involved in DNA metabolic processes to bind. DNA-dependent ATPase A, a 105-kDa protein, was isolated from calf thymus tissue. The human homolog of this protein is known as SMARCAL1. Mutations in this protein causes an autosomal recessive disorder known as Schmike Immuno-osseous Dysplasia (SIOD), which is characterized by renal dysfunction, growth retardation, and spondyloepiphyseal dysplasia. Our main focus is on: Mechanism of ATP hydrolysis: How do the ATP-dependent chromatin remodeling proteins hydrolyze ATP in the presence of DNA? Using variety of biophysical techniques we are beginning to understand the process of DNA-dependent ATP hydrolysis. ADAADi, an inhibitor of the ATP-dependent chromatin remodeling process: ADAADi is generated by enzymatic reaction of aminoglycoside phosphotransferase on aminoglycosides in the presence of ATP. How does it inhibit the ATP-dependent chromatin remodeling process? Can it be used as a therapeutic molecule? Exploring the role of SMARCAL1: What does the protein do in the cell? How is it regulated? What happens in cancer cells? PUBLICATIONS: Ashraf, M., Yadav, B., Sreejith, P., Kumar, S. K., Vats, D., Muthuswami, R. and Komath, S.S. (2011), The N-acetyl-D-glucosaminylphosphotidylinositol de-N-acetylase from Entamoeba histolytica: Metal alters catalytic rates but not substrate affinity. J. Biol. Chem., 286: 2543-2549. Nongkhlaw, M., Dutta, P., Hockensmith, J.W., Komath, S.S., and Muthuswami, R., Elucidating the mechanism of DNA-dependent ATP hydrolysis by DNA-dependent ATPase A, a member of the SWI2/SNF2 protein family (2009). Nucleic Acids Res. 37, 3332-41. Oswal, N., Sahni, N.S., Bhattacharya, A., Komath, S.S., Muthuswami, R., (2008), Unique motifs identify PIG-A proteins from glycosyltransferases of the GT4 family. BMC Evol Biol. 8, 168 Muthuswami, R., Burnett, B.B., Thimmig, R.L., and McHenry, C.S., (2002) The HIV Plus-Strand Transfer Reaction: Stimulation by Nucleocapsid Protein and Identification of a Novel Lentiviral Element, the Primer Overextension Sequence, J. Mol. Biol., 315, 311-23# Muthuswami, R.., Truman, P.A., Mesner, L.D., and Hockensmith, J.W., (2000), A Eukaryotic SWI2/SNF2 Domain, an Exquisite Detector of Double-stranded to Single-stranded DNA Transition Elements, J.Biol.Chem., 275, 7648-7655. Muthuswami, R.., Mesner, L.D., Wang, D., Hill, D.A., Imbalzano, A.N., and Hockensmith, J.W., (2000), Phosphoaminoglycosides Inhibit SWI2/SNF2 Family of DNA-dependent Molecular Motor Domains, Biochemistry, 39, 4358-4365.

ATP-dependent chromatin remodelling is essential for DNA replication, repair, transcription, and recombination. The process uses the energy released by hydrolysis of ATP to move nucleosomes across the DNA, making it accessible for proteins involved in DNA metabolic processes to bind.

DNA-dependent ATPase A, a 105-kDa protein, was isolated from calf thymus tissue. The human homolog of this protein is known as SMARCAL1. Mutations in this protein causes an autosomal recessive disorder known as Schmike Immuno-osseous Dysplasia (SIOD), which is characterized by renal dysfunction, growth retardation, and spondyloepiphyseal dysplasia.

Our main focus is on:

Mechanism of ATP hydrolysis: How do the ATP-dependent chromatin remodeling proteins hydrolyze ATP in the presence of DNA? Using variety of biophysical techniques we are beginning to understand the process of DNA-dependent ATP hydrolysis.

ADAADi, an inhibitor of the ATP-dependent chromatin remodeling process: ADAADi is generated by enzymatic reaction of aminoglycoside phosphotransferase on aminoglycosides in the presence of ATP. How does it inhibit the ATP-dependent chromatin remodeling process? Can it be used as a therapeutic molecule?

Exploring the role of SMARCAL1: What does the protein do in the cell? How is it regulated? What happens in cancer cells?

PUBLICATIONS:

Ashraf, M., Yadav, B., Sreejith, P., Kumar, S. K., Vats, D., Muthuswami, R. and Komath, S.S. (2011), The N-acetyl-D-glucosaminylphosphotidylinositol de-N-acetylase from Entamoeba histolytica: Metal alters catalytic rates but not substrate affinity. J. Biol. Chem., 286: 2543-2549.
Nongkhlaw, M., Dutta, P., Hockensmith, J.W., Komath, S.S., and Muthuswami, R., Elucidating the mechanism of DNA-dependent ATP hydrolysis by DNA-dependent ATPase A, a member of the SWI2/SNF2 protein family (2009). Nucleic Acids Res. 37, 3332-41.
Oswal, N., Sahni, N.S., Bhattacharya, A., Komath, S.S., Muthuswami, R., (2008), Unique motifs identify PIG-A proteins from glycosyltransferases of the GT4 family. BMC Evol Biol. 8, 168
Muthuswami, R., Burnett, B.B., Thimmig, R.L., and McHenry, C.S., (2002) The HIV Plus-Strand Transfer Reaction: Stimulation by Nucleocapsid Protein and Identification of a Novel Lentiviral Element, the Primer Overextension Sequence, J. Mol. Biol., 315, 311-23#
Muthuswami, R.., Truman, P.A., Mesner, L.D., and Hockensmith, J.W., (2000), A Eukaryotic SWI2/SNF2 Domain, an Exquisite Detector of Double-stranded to Single-stranded DNA Transition Elements, J.Biol.Chem., 275, 7648-7655.
Muthuswami, R.., Mesner, L.D., Wang, D., Hill, D.A., Imbalzano, A.N., and Hockensmith, J.W., (2000), Phosphoaminoglycosides Inhibit SWI2/SNF2 Family of DNA-dependent Molecular Motor Domains, Biochemistry, 39, 4358-4365.