Human RPA activates BLM’s bidirectional DNA unwinding from a nick

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 singl...

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Bibliographic Details
Published in:eLife Vol. 9
Main Authors: Qin, Zhenheng, Bi, Lulu, Hou, Xi-Miao, Zhang, Siqi, Zhang, Xia, Lu, Ying, Li, Ming, Modesti, Mauro, Xi, Xu-Guang, Sun, Bo
Format: Journal Article
Language:English
Published: England eLife Science Publications, Ltd 26.02.2020
eLife Sciences Publications Ltd
eLife Sciences Publication
eLife Sciences Publications, Ltd
Subjects:
BLM
Cellular Biology
Deoxyribonucleic acid
DNA
DNA biosynthesis
DNA Breaks, Single-Stranded
DNA damage
DNA helicase
DNA repair
DNA replication
DNA Topoisomerases, Type I - metabolism
DNA unwinding
DNA, Single-Stranded - metabolism
Genomes
Genomics
helicase
Life Sciences
Microscopy
Novels
optical tweezers
Proteins
RecQ Helicases - metabolism
Replication protein A
Replication Protein A - metabolism
RPA
single molecule
Structural Biology and Molecular Biophysics
Unwinding
single molecule
BLM
RPA
chicken
optical tweezers
structural biology
helicase
molecular biophysics
DNA unwinding
ISSN:2050-084X, 2050-084X
Online Access:Get full text
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Summary: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.
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These authors contributed equally to this work.
ISSN:2050-084X
2050-084X
DOI:10.7554/eLife.54098