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Single-molecule imaging of UvrA and UvrB recruitment to DNA lesions in living Escherichia coli

Abstract:
Nucleotide excision repair (NER) removes chemically diverse DNA lesions in all domains of life. In Escherichia coli, UvrA and UvrB initiate NER, although the mechanistic details of how this occurs in vivo remain to be established. Here we provide, using single-molecule fluorescence imaging, a comprehensive characterization of the lesion search, recognition and verification process in living cells. We show that NER initiation involves a two-step mechanism in which UvrA scans the genome and locates DNA damage independently of UvrB. Then UvrA recruits UvrB from solution to the lesion. These steps are coordinated by ATP binding and hydrolysis in the ‘proximal’ and ‘distal’ UvrA ATP-binding sites. We show that initial UvrB-independent damage recognition by UvrA requires ATPase activity in the distal site only. Subsequent UvrB recruitment requires ATP hydrolysis in the proximal site. Finally, UvrA is dissociated from the lesion complex, allowing UvrB to orchestrate the downstream NER reactions.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1038/ncomms12568

Authors


More by this author
Institution:
University of Oxford
Division:
MPLS
Department:
Physics
Sub department:
Condensed Matter Physics
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Biochemistry
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MPLS
Department:
Physics
Sub department:
Condensed Matter Physics
Role:
Author


More from this funder
Funding agency for:
Uphoff, S
Grant:
Junior Research Fellowship
More from this funder
Funding agency for:
Uphoff, S
Grant:
Junior Research Fellowship


Publisher:
Nature Publishing Group
Journal:
Nature Communications More from this journal
Volume:
7
Article number:
12568
Publication date:
2016-08-26
Acceptance date:
2016-07-14
DOI:
ISSN:
2041-1723


Pubs id:
pubs:636302
UUID:
uuid:8dd0f729-31fb-4540-9a1b-021d41dc7144
Local pid:
pubs:636302
Source identifiers:
636302
Deposit date:
2016-07-28

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