UMMS Affiliation

Department of Cancer Biology

Date

12-6-2006

Document Type

Article

Subjects

Adenosine Triphosphatases; Amino Acid Sequence; Basic-Leucine Zipper Transcription Factors; Catalysis; DNA; DNA Helicases; DNA, Single-Stranded; Fanconi Anemia Complementation Group; Proteins; Humans; Molecular Sequence Data; Polymorphism, Genetic; Protein Structure, Tertiary

Abstract

The BRCA1 associated C-terminal helicase (BACH1) associated with breast cancer has been implicated in double strand break (DSB) repair. More recently, BACH1 (FANCJ) has been genetically linked to the chromosomal instability disorder Fanconi Anemia (FA). Understanding the roles of BACH1 in cellular DNA metabolism and how BACH1 dysfunction leads to tumorigenesis requires a comprehensive investigation of its catalytic mechanism and molecular functions in DNA repair. In this study, we have determined that BACH1 helicase contacts with both the translocating and the non-translocating strands of the duplex are critical for its ability to track along the sugar phosphate backbone and unwind dsDNA. An increased motor ATPase of a BACH1 helicase domain variant (M299I) enabled the helicase to unwind the backbone-modified DNA substrate in a more proficient manner. Alternatively, increasing the length of the 5' tail of the DNA substrate allowed BACH1 to overcome the backbone discontinuity, suggesting that BACH1 loading mechanism is critical for its ability to unwind damaged DNA molecules.

Rights and Permissions

Citation: Nucleic Acids Res. 2006;34(22):6673-83. Epub 2006 Dec 1. Link to article on publisher's site

Related Resources

Link to Article in PubMed

PubMed ID

17145708

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