Cited by 131DNA Repair MechanismsDNA and Nucleic Acid ChemistryBRCA gene mutations in cancer

Analysis of the DNA Substrate Specificity of the Human BACH1 HelicaseAssociated with BreastCancer

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Gupta, Rigu, Sharma, Sudha, Sommers, Joshua A., Jin, Zhe, Cantor, Sharon B., Brosh, Robert M.·2005·Journal of Biological Chemistry

Abstract

We have investigated the DNA substrate specificity of BACH1 (BRCA1-associated C-terminal helicase). The importance of various DNA structural elements for efficient unwinding by purified recombinant BACH1 helicase was examined. The results indicated that BACH1 preferentially binds and unwinds a forked duplex substrate compared with a duplex flanked by only one single-stranded DNA (ssDNA) tail. In support of its DNA substrate preference, helicase sequestration studies revealed that BACH1 can be preferentially trapped by forked duplex molecules. BACH1 helicase requires a minimal 5 ' ssDNA tail of 15 nucleotides for unwinding of conventional duplex DNA substrates; however, the enzyme is able to catalytically release the third strand of the homologous recombination intermediate D-loop structure irrespective of DNA tail status. In contrast, BACH1 completely fails to unwind a synthetic Holliday junction structure. Moreover, BACH1 requires nucleic acid continuity in the 5 ' ssDNA tail of the forked duplex substrate within six nucleotides of the ssDNA-dsDNA junction to initiate efficiently DNA unwinding. These studies provide the first detailed information on the DNA substrate specificity of BACH1 helicase and provide insight to the types of DNA structures the enzyme is likely to act upon to perform its functions in DNA repair or recombination.

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Crossref · 10.1074/jbc.m501995200

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  • FANCJ preferentially binds and unwinds forked duplex DNA substrates and D-loop structures that mimic a homologous recombination intermediate.

    “Moreover, it was determined that FANCJ preferentially binds and unwinds forked duplex DNA substrates as well as D-loop structures that mimic an intermediate step in homologous recombination [61].”
  • The ATPase and helicase functions of FANCJ are inactivated by the K52R missense mutation in the ATP-binding pocket.

    “As predicted, the ATPase and helicase functions were inactivated by a single missense mutation (K52R) in the ATP-binding pocket of the FANCJ helicase domain [56,61,62].”
  • The P47A FANCJ mutant has disrupted enzyme activity.

    “The P47A mutant had disrupted enzyme activity”
  • The M299I FANCJ mutant has enhanced ATPase, helicase, and translocase activity.

    “the M299I mutant had enhanced ATPase, helicase and translocase activity [56,61]”

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Research works printed but not linked: 2

  1. Cantor, S., Drapkin, R., Zhang, F., Lin, Y., Han, J., Pamidi, S., and Livingston, D. M. (2004) Proc. Natl. Acad. Sci. U. S. A. 101, 2357-2362
  2. Paull, T. T., Cortez, D., Bowers, B., Elledge, S. J., and Gellert, M. (2001) Proc. Natl. Acad. Sci. U. S. A. 98, 6086 -6091

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Authors
Gupta, R., Sharma, S., Sommers, J. A., Jin, Z., Cantor, S. B., & Brosh, R. M.
Affiliations
  • National Institutes of Health (US)
  • University of Massachusetts Chan Medical School (US)
Corresponding author
Brosh, Robert M.
Venue
Journal of Biological Chemistry
Publisher
Elsevier BV
Published
2005-07
Volume
280
Issue
27
Pages
25450-25460
ISSN
0021-9258 (ISSN-L)
OpenAlex
W1986550902
Cited by
131
References
31
Citations by year
2026: 3 · 2025: 3 · 2024: 4 · 2023: 5 · 2022: 3 · 2021: 3 · 2020: 6 · 2019: 2 · 2018: 3 · 2017: 3 · 2016: 5 · 2015: 8 · 2014: 5 · 2013: 4 · 2012: 6
FWCI
3.64
Type
journal article
Language
en
Open access
Locations
  • Journal of Biological Chemistry (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • The Journal of the American Medical Association (JAMA) Network (American Medical Association) (submittedVersion)
Funders
  • National Institutes of Health
  • National Institute on Aging
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA and Nucleic Acid Chemistry
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › BRCA gene mutations in cancer
Keywords
DNA unwinding, homologous recombination, Holliday junction, DNA repair, breast cancer
MeSH terms
Breast Neoplasms, DNA, DNA Helicases, DNA, Single-Stranded, Enzyme Activation, Humans, Nucleic Acid Conformation, Substrate Specificity, Transcription Factors, DNA, Cruciform, Basic-Leucine Zipper Transcription Factors, Fanconi Anemia Complementation Group Proteins

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