FANCJ Uses Its Motor ATPase to Destabilize Protein-DNA Complexes, Unwind Triplexes, and Inhibit RAD51 Strand Exchange

• Published in: The Journal of biological chemistry 2009-03, Vol.284 (12), p.7505-7517
• Main Authors: Sommers, Joshua A., Rawtani, Nina, Gupta, Rigu, Bugreev, Dmitry V., Mazin, Alexander V., Cantor, Sharon B., Brosh, Robert M.
• Format: Article
• Language: English
• Subjects: Adenosine Triphosphatases - genetics; Adenosine Triphosphatases - metabolism; Adenosine Triphosphate - genetics; Adenosine Triphosphate - metabolism; Basic-Leucine Zipper Transcription Factors - genetics; Basic-Leucine Zipper Transcription Factors - metabolism; DNA - genetics; DNA - metabolism; DNA Breaks, Double-Stranded; DNA Repair - physiology; DNA Replication - physiology; DNA: , Repair, Recombination, and Chromosome Dynamics; Fanconi Anemia Complementation Group Proteins - genetics; Fanconi Anemia Complementation Group Proteins - metabolism; Female; Humans; Hydrolysis; Rad51 Recombinase - genetics; Rad51 Recombinase - metabolism; Recombination, Genetic - physiology
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M809019200

Mutations in the FANCJ helicase predispose individuals to breast cancer and are genetically linked to the Fanconi anemia (FA) complementation group J. FA is a chromosomal instability disorder characterized by multiple congenital anomalies, progressive bone marrow failure, and high cancer risk. FANCJ has been proposed to function downstream of FANCD2 monoubiquitination, a critical event in the FA pathway. Evidence supports a role for FANCJ in a homologous recombination pathway of double strand break repair. In an effort to understand the molecular functions of FANCJ, we have investigated the ability of purified FANCJ recombinant protein to use its motor ATPase function for activities in addition to unwinding of conventional duplex DNA substrates. These efforts have led to the discovery that FANCJ ATP hydrolysis can be used to destabilize protein-DNA complexes and unwind triple helix alternate DNA structures. These novel catalytic functions of FANCJ may be important for its role in cellular DNA repair, recombination, or resolving DNA structural obstacles to replication. Consistent with this, we show that FANCJ can inhibit RAD51 strand exchange, an activity that is likely to be important for its role in controlling DNA repair through homologous recombination.