Publication Date:
2014-01-10
Description:
UvrD helicase is required for nucleotide excision repair, although its role in this process is not well defined. Here we show that Escherichia coli UvrD binds RNA polymerase during transcription elongation and, using its helicase/translocase activity, forces RNA polymerase to slide backward along DNA. By inducing backtracking, UvrD exposes DNA lesions shielded by blocked RNA polymerase, allowing nucleotide excision repair enzymes to gain access to sites of damage. Our results establish UvrD as a bona fide transcription elongation factor that contributes to genomic integrity by resolving conflicts between transcription and DNA repair complexes. Furthermore, we show that the elongation factor NusA cooperates with UvrD in coupling transcription to DNA repair by promoting backtracking and recruiting nucleotide excision repair enzymes to exposed lesions. Because backtracking is a shared feature of all cellular RNA polymerases, we propose that this mechanism enables RNA polymerases to function as global DNA damage scanners in bacteria and eukaryotes.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4471481/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4471481/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Epshtein, Vitaly -- Kamarthapu, Venu -- McGary, Katelyn -- Svetlov, Vladimir -- Ueberheide, Beatrix -- Proshkin, Sergey -- Mironov, Alexander -- Nudler, Evgeny -- R01 GM058750/GM/NIGMS NIH HHS/ -- T32 GM088118/GM/NIGMS NIH HHS/ -- Howard Hughes Medical Institute/ -- England -- Nature. 2014 Jan 16;505(7483):372-7. doi: 10.1038/nature12928. Epub 2014 Jan 8.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉1] Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York 10016, USA [2]. ; 1] Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York 10016, USA [2] Howard Hughes Medical Institute, New York University School of Medicine, New York, New York 10016, USA [3]. ; Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York 10016, USA. ; State Research Institute of Genetics and Selection of Industrial Microorganisms, Moscow 117545, Russia. ; 1] State Research Institute of Genetics and Selection of Industrial Microorganisms, Moscow 117545, Russia [2] Engelhardt Institute of Molecular Biology, Russian Academy of Science, Moscow 119991, Russia. ; 1] Department of Biochemistry and Molecular Pharmacology, New York University School of Medicine, New York, New York 10016, USA [2] Howard Hughes Medical Institute, New York University School of Medicine, New York, New York 10016, USA.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/24402227" target="_blank"〉PubMed〈/a〉
Keywords:
Base Sequence
;
DNA/chemistry/metabolism
;
DNA Damage
;
DNA Helicases/*metabolism
;
*DNA Repair
;
DNA-Directed RNA Polymerases/chemistry/*metabolism
;
Escherichia coli/enzymology/genetics
;
Escherichia coli Proteins/*metabolism
;
Models, Molecular
;
Molecular Sequence Data
;
*Movement
;
Peptide Elongation Factors/metabolism
;
Protein Binding
;
Transcription Factors/metabolism
;
Transcription, Genetic
;
Transcriptional Elongation Factors
Print ISSN:
0028-0836
Electronic ISSN:
1476-4687
Topics:
Biology
,
Chemistry and Pharmacology
,
Medicine
,
Natural Sciences in General
,
Physics
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