Homology sensing via non-linear amplification of sequence-dependent pausing by RecQ helicase.
E. coli
biochemistry
chemical biology
genome stability
helicase
homologous recombination
magnetic tweezers
molecular biophysics
single molecule biophysics
structural biology
unwinding mechanism
Journal
eLife
ISSN: 2050-084X
Titre abrégé: Elife
Pays: England
ID NLM: 101579614
Informations de publication
Date de publication:
29 08 2019
29 08 2019
Historique:
received:
08
02
2019
accepted:
28
08
2019
pubmed:
30
8
2019
medline:
12
2
2020
entrez:
30
8
2019
Statut:
epublish
Résumé
RecQ helicases promote genomic stability through their unique ability to suppress illegitimate recombination and resolve recombination intermediates. These DNA structure-specific activities of RecQ helicases are mediated by the helicase-and-RNAseD like C-terminal (HRDC) domain, via unknown mechanisms. Here, employing single-molecule magnetic tweezers and rapid kinetic approaches we establish that the HRDC domain stabilizes intrinsic, sequence-dependent, pauses of the core helicase (lacking the HRDC) in a DNA geometry-dependent manner. We elucidate the core unwinding mechanism in which the unwinding rate depends on the stability of the duplex DNA leading to transient sequence-dependent pauses. We further demonstrate a non-linear amplification of these transient pauses by the controlled binding of the HRDC domain. The resulting DNA sequence- and geometry-dependent pausing may underlie a homology sensing mechanism that allows rapid disruption of unstable (illegitimate) and stabilization of stable (legitimate) DNA strand invasions, which suggests an intrinsic mechanism of recombination quality control by RecQ helicases.
Identifiants
pubmed: 31464683
doi: 10.7554/eLife.45909
pii: 45909
pmc: PMC6773442
doi:
pii:
Substances chimiques
DNA
9007-49-2
RecQ Helicases
EC 3.6.4.12
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Human Frontier Science Program
ID : RGY0072/2010
Pays : International
Organisme : NIH HHS
ID : HL001056-12
Pays : United States
Organisme : Hungarian Academy of Sciences
ID : LP2011-006/2011
Pays : International
Organisme : Eötvös Loránd University
ID : ELTE KMOP-4.2.1/B-10-2011-0002
Pays : International
Organisme : Nemzeti Kutatási és Technológiai Hivatal
ID : NKFIH K-116072
Pays : International
Organisme : Nemzeti Kutatási és Technológiai Hivatal
ID : NKFIH ERC_HU 117680
Pays : International
Organisme : Nemzeti Kutatási és Technológiai Hivatal
ID : NKFIH K-123989
Pays : International
Organisme : NIH HHS
ID : HL001056-12
Pays : United States
Déclaration de conflit d'intérêts
YS, GH, MK, KN No competing interests declared
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