UMMS Affiliation
Department of Cancer Biology
Publication Date
2006-12-06
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
Disciplines
Cancer Biology | Neoplasms
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.
DOI of Published Version
10.1093/nar/gkl964
Source
Nucleic Acids Res. 2006;34(22):6673-83. Epub 2006 Dec 1. Link to article on publisher's site
Journal/Book/Conference Title
Nucleic acids research
Related Resources
PubMed ID
17145708
Repository Citation
Gupta, Rigu; Sharma, Sudha; Doherty, Kevin M.; Sommers, Joshua A.; Cantor, Sharon B.; and Brosh, Robert M., "Inhibition of BACH1 (FANCJ) helicase by backbone discontinuity is overcome by increased motor ATPase or length of loading strand" (2006). Cancer Biology Publications and Presentations. 2.
https://escholarship.umassmed.edu/cancerbiology_pp/2