Robert M. Brosh Jr., Ph.D.

Senior Investigator

Laboratory of Molecular Gerontology

NIA

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251 Bayview Boulevard
Suite 100
Baltimore, MD 21224

410-558-8578

broshr@mail.nih.gov

Research Topics

Roles of DNA Helicases in Genomic Stability: The growing number of DNA helicases implicated in human disease suggests that these enzymes have vital specialized roles during replication, DNA repair, recombination, and transcription. We and others have shown that both Werner (WRN) and Bloom (BLM) gene products are helicases, suggesting that basic defects in DNA metabolic pathways give rise to the aberrant cellular and clinical phenotypes of the premature aging disorder Werner Syndrome (WS) and cancer predisposition disorder Bloom Syndrome (BS). Cellular studies and biochemical data are consistent with this notion; however, the precise molecular functions of the sequence-related WRN and BLM proteins remain to be defined. Defining the biochemical functions of DNA helicases will help us to understand molecular defects associated with aging and cancer.

Biography

Dr. Robert Brosh received his M.S. in biochemistry from Texas A & M University in 1988 and his Ph.D. in biology from the University of North Carolina at Chapel Hill in 1996. He did postdoctoral work at NIH before assuming his present position in the Laboratory of Molecular Genetics, NIA.

Selected Publications

  1. Bharti SK, Sommers JA, Awate S, Bellani MA, Khan I, Bradley L, King GA, Seol Y, Vidhyasagar V, Wu Y, Abe T, Kobayashi K, Shin-Ya K, Kitao H, Wold MS, Branzei D, Neuman KC, Brosh RM Jr. A minimal threshold of FANCJ helicase activity is required for its response to replication stress or double-strand break repair. Nucleic Acids Res. 2018;46(12):6238-6256.

  2. Khan I, Crouch JD, Bharti SK, Sommers JA, Carney SM, Yakubovskaya E, Garcia-Diaz M, Trakselis MA, Brosh RM Jr. Biochemical Characterization of the Human Mitochondrial Replicative Twinkle Helicase: SUBSTRATE SPECIFICITY, DNA BRANCH MIGRATION, AND ABILITY TO OVERCOME BLOCKADES TO DNA UNWINDING. J Biol Chem. 2016;291(27):14324-39.

  3. Banerjee T, Sommers JA, Huang J, Seidman MM, Brosh RM Jr. Catalytic strand separation by RECQ1 is required for RPA-mediated response to replication stress. Curr Biol. 2015;25(21):2830-2838.

  4. Brosh RM Jr. DNA helicases involved in DNA repair and their roles in cancer. Nat Rev Cancer. 2013;13(8):542-58.

  5. Aggarwal M, Sommers JA, Shoemaker RH, Brosh RM Jr. Inhibition of helicase activity by a small molecule impairs Werner syndrome helicase (WRN) function in the cellular response to DNA damage or replication stress. Proc Natl Acad Sci U S A. 2011;108(4):1525-30.

Related Scientific Focus Areas

This page was last updated on August 21st, 2018