Human RPA activates BLM's bidirectional DNA unwinding from a nick.


Journal

eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614

Informations de publication

Date de publication:
26 02 2020
Historique:
received: 02 12 2019
accepted: 25 02 2020
pubmed: 27 2 2020
medline: 10 4 2021
entrez: 27 2 2020
Statut: epublish

Résumé

BLM is a multifunctional helicase that plays critical roles in maintaining genome stability. It processes distinct DNA substrates, but not nicked DNA, during many steps in DNA replication and repair. However, how BLM prepares itself for diverse functions remains elusive. Here, using a combined single-molecule approach, we find that a high abundance of BLMs can indeed unidirectionally unwind dsDNA from a nick when an external destabilizing force is applied. Strikingly, human replication protein A (hRPA) not only ensures that limited quantities of BLMs processively unwind nicked dsDNA under a reduced force but also permits the translocation of BLMs on both intact and nicked ssDNAs, resulting in a bidirectional unwinding mode. This activation necessitates BLM targeting on the nick and the presence of free hRPAs in solution whereas direct interactions between them are dispensable. Our findings present novel DNA unwinding activities of BLM that potentially facilitate its function switching in DNA repair.

Identifiants

pubmed: 32101168
doi: 10.7554/eLife.54098
pii: 54098
pmc: PMC7065910
doi:
pii:

Substances chimiques

DNA, Single-Stranded 0
Replication Protein A 0
Bloom syndrome protein EC 3.6.1.-
RecQ Helicases EC 3.6.4.12
DNA Topoisomerases, Type I EC 5.99.1.2

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Subventions

Organisme : Ministry of Science and Technology of the People's Republic of China
ID : 2016YFA0500902
Organisme : Ministry of Science and Technology of the People's Republic of China
ID : 2017YFA0106700
Organisme : Shanghai Natural Science Foundation
ID : 19ZR1434100
Organisme : Institut National Du Cancer
ID : PLBIO2017-167
Organisme : The French National League Against Cancer
ID : EL2028.LNCC/MaM
Organisme : The Natural Science Foundation of Shanghai
ID : 19ZR1434100
Organisme : The French National Cancer Institute
ID : PLBIO2017-167

Informations de copyright

© 2020, Qin et al.

Déclaration de conflit d'intérêts

ZQ, LB, XH, SZ, XZ, YL, ML, MM, XX, BS No competing interests declared

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Auteurs

Zhenheng Qin (Z)

School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China.
University of Chinese Academy of Sciences, Beijing, China.

Lulu Bi (L)

School of Life Science and Technology, ShanghaiTech University, Shanghai, China.

Xi-Miao Hou (XM)

College of Life Sciences, Northwest A&F University, Yangling, China.

Siqi Zhang (S)

School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
Shanghai Institute of Biochemistry and Cell Biology, Chinese Academy of Sciences, Shanghai, China.
University of Chinese Academy of Sciences, Beijing, China.

Xia Zhang (X)

School of Life Science and Technology, ShanghaiTech University, Shanghai, China.

Ying Lu (Y)

Institute of Physics, Chinese Academy of Sciences, Beijing, China.

Ming Li (M)

University of Chinese Academy of Sciences, Beijing, China.
Institute of Physics, Chinese Academy of Sciences, Beijing, China.

Mauro Modesti (M)

Cancer Research Center of Marseille, CNRS UMR7258, Inserm U1068, Institut Paoli-Calmettes, Aix-Marseille Université, Marseille, France.

Xu-Guang Xi (XG)

The LBPA, Ecole Normale Supérieure Paris-Saclay, CNRS, Université Paris Saclay, Gif-sur-Yvette, France.

Bo Sun (B)

School of Life Science and Technology, ShanghaiTech University, Shanghai, China.

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Classifications MeSH