Our recent work has focused on the roles of the FANCJ helicase in the DNA damage response. Mutations in the BRCA1-associated helicase BACH1 have been associated with early-onset breast cancer and cellular data suggest a role of the helicase in double strand break repair and checkpoint control. Recently, BACH1 (FANCJ) has been genetically linked to the chromosomal instability disorder Fanconi anemia (FA). To understand the molecular functions and biological substrates that FANCJ helicase acts upon, we have systematically evaluated the ability of purified recombinant FANCJ to unwind a panel of related DNA substrates with distinct tail variations including single-stranded versus double-stranded character, tail length, or backbone continuity. In addition, we have assessed the ability of BACH1 to catalytically unwind DNA structures proposed to be key intermediates of cellular DNA metabolism. The results from these unwinding studies provide a platform to investigate the molecular interactions of the FANCJ helicase with its protein partners in double strand break repair by homologous recombination. In terms of protein interactions, we have identified and characterized two novel FANCJ partners, the mismatch repair protein complex MutL alpha and the single-stranded DNA binding protein RPA. FANCJ interactions with these DNA repair factors play important roles in the DNA damage response. Our current efforts are directed toward understanding the roles of FANCJ in the classic FA pathway of cross-link repair as well as stabilization and progression of the replication fork.

National Institute of Health (NIH)
National Institute on Aging (NIA)
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National Institute on Aging
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Bharti, Sanjay Kumar; Khan, Irfan; Banerjee, Taraswi et al. (2014) Molecular functions and cellular roles of the ChlR1 (DDX11) helicase defective in the rare cohesinopathy Warsaw breakage syndrome. Cell Mol Life Sci 71:2625-39
Sommers, Joshua A; Banerjee, Taraswi; Hinds, Twila et al. (2014) Novel function of the Fanconi anemia group J or RECQ1 helicase to disrupt protein-DNA complexes in a replication protein A-stimulated manner. J Biol Chem 289:19928-41
Henderson, Alexander; Wu, Yuliang; Huang, Yu Chuan et al. (2014) Detection of G-quadruplex DNA in mammalian cells. Nucleic Acids Res 42:860-9
Capo-Chichi, José-Mario; Bharti, Sanjay Kumar; Sommers, Joshua A et al. (2013) Identification and biochemical characterization of a novel mutation in DDX11 causing Warsaw breakage syndrome. Hum Mutat 34:103-7
Suhasini, Avvaru N; Brosh Jr, Robert M (2013) DNA helicases associated with genetic instability, cancer, and aging. Adv Exp Med Biol 767:123-44
Brosh Jr, Robert M (2013) DNA helicases involved in DNA repair and their roles in cancer. Nat Rev Cancer 13:542-58
Suhasini, Avvaru N; Brosh Jr, Robert M (2013) Disease-causing missense mutations in human DNA helicase disorders. Mutat Res 752:138-52
Banerjee, Taraswi; Aggarwal, Monika; Brosh Jr, Robert M (2013) A new development in DNA repair modulation: discovery of a BLM helicase inhibitor. Cell Cycle 12:713-4
Bharti, Sanjay Kumar; Sommers, Joshua A; George, Fourbears et al. (2013) Specialization Among Iron-Sulfur Cluster Helicases to Resolve G-Quadruplex DNA Structures that Threaten Genomic Stability. J Biol Chem :
Suhasini, Avvaru N; Sommers, Joshua A; Muniandy, Parameswary A et al. (2013) Fanconi anemia group J helicase and MRE11 nuclease interact to facilitate the DNA damage response. Mol Cell Biol 33:2212-27

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