Bloom's syndrome protein unfolding G-quadruplexes in two pathways

doi:10.1088/1674-1056/26/8/088701

Abstract

The Bloom helicase (BLM) gene product encodes a DNA helicase that functions in homologous recombination repair to prevent genomic instability. BLM is highly active in binding and unfolding G-quadruplexes (G4), which are non-canonical DNA structures formed by Hoogsteen base-pairing in guanine-rich sequences. Here we use single-molecule fluorescence resonance energy transfer (smFRET) to study the molecular mechanism of BLM-catalysed G4 unfolding and show that BLM unfolds G4 in two pathways. Our data enable us to propose a model in which the HRDC domain functions as a regulator of BLM, depending on the position of the HRDC domain of BLM in action: when HRDC binds to the G4 sequence, BLM may hold G4 in the unfolded state; otherwise, it may remain on the unfolded G4 transiently so that G4 can refold immediately.

Keywords: G-quadruplexes BLM helicase smFRET

Received: 24 March 2017
Revised: 12 April 2017
Accepted manuscript online:

PACS:	87.14.G-	(Nucleic acids)
	87.15.H-	(Dynamics of biomolecules)
	87.15.kj	(Protein-polynucleotide interactions)

Fund:

Project supported by the National Natural Science Foundation of China (Grant Nos. 11674382, 11574381, and 11574382) and the Key Research Program of Frontier Sciences, Chinese Academy of Sciences (Grant No. QYZDJ-SSW-SYS014).

Corresponding Authors: Ying Lu
E-mail: yinglu@iphy.ac.cn

About author: 0.1088/1674-1056/26/8/

Cite this article:

Zhen-Ye Zhao(赵振业), Chun-Hua Xu(徐春华), Jing Shi(史婧), Jing-Hua Li(李菁华), Jian-Bing Ma(马建兵), Qi Jia(贾棋), Dong-Fei Ma(马东飞), Ming Li(李明), Ying Lu(陆颖) Bloom's syndrome protein unfolding G-quadruplexes in two pathways 2017 Chin. Phys. B 26 088701

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Bloom's syndrome protein unfolding G-quadruplexes in two pathways

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