RQC helical hairpin in Bloom's syndrome helicase regulates DNA unwinding by dynamically intercepting nascent nucleotides
Jianbing Ma,
Chunhua Xu,
Jinghua Li,
Xi-Miao Hou,
Lin-Tai Da,
Qi Jia,
Xingyuan Huang,
Jin Yu,
Xuguang Xi,
Ying Lu,
Ming Li
Affiliations
Jianbing Ma
Songshan Lake Materials Laboratory, Dongguan, Guangdong 523808, China; Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China
Chunhua Xu
Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China
Jinghua Li
Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China
Xi-Miao Hou
College of Life Sciences, Northwest A&F University, Yangling 712100, Shaanxi, China
Lin-Tai Da
Key Laboratory of System Biomedicine (Ministry of Education), Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai 200240, China
Qi Jia
Songshan Lake Materials Laboratory, Dongguan, Guangdong 523808, China; Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, China
Xingyuan Huang
Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, China
Jin Yu
Department of Physics and Astronomy, Department of Chemistry, NSF-Simons Center for Multiscale Cell Fate Research, University of California, Irvine, CA 92697, USA
Songshan Lake Materials Laboratory, Dongguan, Guangdong 523808, China; Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, China; Corresponding author
Ming Li
Songshan Lake Materials Laboratory, Dongguan, Guangdong 523808, China; Beijing National Laboratory for Condensed Matter Physics, Institute of Physics, Chinese Academy of Sciences, Beijing 100190, China; University of Chinese Academy of Sciences, Beijing 100049, China
Summary: The RecQ family of helicases are important for maintenance of genomic integrity. Although functions of constructive subdomains of this family of helicases have been extensively studied, the helical hairpin (HH) in the RecQ-C-terminal domain (RQC) has been underappreciated and remains poorly understood. Here by using single-molecule fluorescence resonance energy transfer, we found that HH in the human BLM transiently intercepts different numbers of nucleotides when it is unwinding a double-stranded DNA. Single-site mutations in HH that disrupt hydrogen bonds and/or salt bridges between DNA and HH change the DNA binding conformations and the unwinding features significantly. Our results, together with recent clinical tests that correlate single-site mutations in HH of human BLM with the phenotype of cancer-predisposing syndrome or Bloom's syndrome, implicate pivotal roles of HH in BLM's DNA unwinding activity. Similar mechanisms might also apply to other RecQ family helicases, calling for more attention to the RQC helical hairpin.
