RecQ-core of BLM unfolds telomeric G-quadruplex in the absence of ATP

0455781 - ÚMG 2016 RIV GB eng J - Článek v odborném periodiku
Budhathoki, J.B. - Ray, S. - Urban, Václav - Janščák, Pavel - Jodh, J.G. - Balci, H.
RecQ-core of BLM unfolds telomeric G-quadruplex in the absence of ATP.
Nucleic Acids Research. Roč. 42, č. 18 (2014), s. 11528-11545. ISSN 0305-1048. E-ISSN 1362-4962
Grant CEP: GA ČR GA204/09/0565
Grant ostatní: U.S. National Science Foundation through the Physics Frontiers Center Program(US) 1430124
Institucionální podpora: RVO:68378050
Klíčová slova: single-stranded DNA * RECQ5 helicase * G-quadruplex structures
Kód oboru RIV: EB - Genetika a molekulární biologie
Impakt faktor: 9.112, rok: 2014

Various helicases and single-stranded DNA (ss-DNA) binding proteins are known to destabilize G-quadruplex (GQ) structures, which otherwise result in genomic instability. Bulk biochemical studies have shown that Bloom helicase (BLM) unfolds both intermolecular and intramolecular GQ in the presence of ATP. Using single molecule FRET, we show that binding of RecQ-core of BLM (will be referred to as BLM) to ssDNA in the vicinity of an intramolecular GQ leads to destabilization and unfolding of the GQ in the absence of ATP. We show that the efficiency of BLM-mediated GQ unfolding correlates with the binding stability of BLM to ssDNA overhang, as modulated by the nucleotide state, ionic conditions, overhang length and overhang directionality. In particular, we observed enhanced GQ unfolding by BLM in the presence of non-hydrolysable ATP analogs, which has implications for the underlying mechanism. We also show that increasing GQ stability, via shorter loops or higher ionic strength, reduces BLM-mediated GQ unfolding. Finally, we show that while WRN has similar activity as BLM, RecQ and RECQ5 helicases do not unfold GQ in the absence of ATP at physiological ionic strength. In summary, our study points to a novel and potentially very common mechanism of GQ destabilization mediated by proteins binding to the vicinity of these structures.
Trvalý link: http://hdl.handle.net/11104/0256404