dc.contributor.author
Roske, Johann J.
dc.contributor.author
Liu, Sunbin
dc.contributor.author
Loll, Bernhard
dc.contributor.author
Neu, Ursula
dc.contributor.author
Wahl, Markus C.
dc.date.accessioned
2021-03-12T15:05:20Z
dc.date.available
2021-03-12T15:05:20Z
dc.identifier.uri
https://refubium.fu-berlin.de/handle/fub188/29920
dc.identifier.uri
http://dx.doi.org/10.17169/refubium-29662
dc.description.abstract
Mitomycin repair factor A represents a family of DNA helicases that harbor a domain of unknown function (DUF1998) and support repair of mitomycin C-induced DNA damage by presently unknown molecular mechanisms. We determined crystal structures of Bacillus subtilis Mitomycin repair factor A alone and in complex with an ATP analog and/or DNA and conducted structure-informed functional analyses. Our results reveal a unique set of auxiliary domains appended to a dual-RecA domain core. Upon DNA binding, a Zn2+-binding domain, encompassing the domain of unknown function, acts like a drum that rolls out a canopy of helicase-associated domains, entrapping the substrate and tautening an inter-domain linker across the loading strand. Quantification of DNA binding, stimulated ATPase and helicase activities in the wild type and mutant enzyme variants in conjunction with the mode of coordination of the ATP analog suggest that Mitomycin repair factor A employs similar ATPase-driven conformational changes to translocate on DNA, with the linker ratcheting through the nucleotides like a 'skipping rope'. The electrostatic surface topology outlines a likely path for the displaced DNA strand. Our results reveal unique molecular mechanisms in a widespread family of DNA repair helicases linked to bacterial antibiotics resistance.
en
dc.format.extent
15 Seiten
dc.rights.uri
https://creativecommons.org/licenses/by-nc/4.0/
dc.subject
RNA helicases
en
dc.subject.ddc
500 Naturwissenschaften und Mathematik::570 Biowissenschaften; Biologie::570 Biowissenschaften; Biologie
dc.title
A skipping rope translocation mechanism in a widespread family of DNA repair helicases
dc.type
Wissenschaftlicher Artikel
dcterms.bibliographicCitation.doi
10.1093/nar/gkaa1174
dcterms.bibliographicCitation.journaltitle
Nucleic Acids Research
dcterms.bibliographicCitation.number
1
dcterms.bibliographicCitation.pagestart
504
dcterms.bibliographicCitation.pageend
518
dcterms.bibliographicCitation.volume
49
dcterms.bibliographicCitation.url
https://doi.org/10.1093/nar/gkaa1174
refubium.affiliation
Biologie, Chemie, Pharmazie
refubium.affiliation.other
Institut für Chemie und Biochemie
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refubium.resourceType.isindependentpub
no
dcterms.accessRights.openaire
open access
dcterms.isPartOf.issn
0305-1048
dcterms.isPartOf.eissn
1362-4962
refubium.resourceType.provider
WoS-Alert