The Q motif of Fanconi anemia group J protein (FANCJ) DNA helicase regulates its dimerization, DNA binding, and DNA repair function.

The Journal of Biological Chemistry
Y WuRobert M Brosh

Abstract

The Q motif, conserved in a number of RNA and DNA helicases, is proposed to be important for ATP binding based on structural data, but its precise biochemical functions are less certain. FANCJ encodes a Q motif DEAH box DNA helicase implicated in Fanconi anemia and breast cancer. A Q25A mutation of the invariant glutamine in the Q motif abolished its ability to complement cisplatin or telomestatin sensitivity of a fancj null cell line and exerted a dominant negative effect. Biochemical characterization of the purified recombinant FANCJ-Q25A protein showed that the mutation disabled FANCJ helicase activity and the ability to disrupt protein-DNA interactions. FANCJ-Q25A showed impaired DNA binding and ATPase activity but displayed ATP binding and temperature-induced unfolding transition similar to FANCJ-WT. Size exclusion chromatography and sedimentation velocity analyses revealed that FANCJ-WT existed as molecular weight species corresponding to a monomer and a dimer, and the dimeric form displayed a higher specific activity for ATPase and helicase, as well as greater DNA binding. In contrast, FANCJ-Q25A existed only as a monomer, devoid of helicase activity. Thus, the Q motif is essential for FANCJ enzymatic activity in vitro a...Continue Reading

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Citations

Jul 12, 2013·Nature Reviews. Cancer·Robert M Brosh
Feb 4, 2014·Cellular and Molecular Life Sciences : CMLS·Sanjay Kumar BhartiRobert M Brosh
Feb 18, 2016·Nucleic Acids Research·Oscar MendozaJean-Louis Mergny
Feb 7, 2015·Biochimica Et Biophysica Acta·Jill O FussJohn A Tainer
Nov 7, 2014·Frontiers in Genetics·Robert M Brosh, Sharon B Cantor
Jan 1, 2014·PloS One·Jonathan P RileyShreevrat Goenka
Jun 28, 2016·Nucleic Acids Research·Colin G Wu, Maria Spies
Jan 2, 2013·Mutation Research·Avvaru N Suhasini, Robert M Brosh
Jul 15, 2015·DNA Repair·Irfan KhanRobert M Brosh
Jun 9, 2017·International Journal of Molecular Sciences·Sanket Awate, Robert M Brosh
Jan 17, 2019·The Journal of Biological Chemistry·Helen HoffmeisterGernot Längst
Aug 13, 2013·The Journal of Biological Chemistry·Sanjay Kumar BhartiRobert M Brosh
Mar 4, 2020·Genes·Robert M Brosh, Steven W Matson
Mar 20, 2020·Human Molecular Genetics·Thomas J ButlerRobert M Brosh
Dec 12, 2019·Cancer Research·Cassandra L MoyerPaul J Goodfellow

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