The iron-sulfur helicase DDX11 promotes the generation of single-stranded DNA for CHK1 activation.
Adenosine Triphosphatases
/ genetics
Animals
Cell Cycle Proteins
/ genetics
Checkpoint Kinase 1
/ genetics
DEAD-box RNA Helicases
/ genetics
DNA
/ chemistry
DNA Helicases
/ genetics
DNA Polymerase III
/ chemistry
DNA Replication
DNA, Single-Stranded
/ biosynthesis
DNA-Binding Proteins
/ metabolism
Humans
Replication Protein A
/ metabolism
Sf9 Cells
Journal
Life science alliance
ISSN: 2575-1077
Titre abrégé: Life Sci Alliance
Pays: United States
ID NLM: 101728869
Informations de publication
Date de publication:
03 2020
03 2020
Historique:
received:
11
09
2019
revised:
06
02
2020
accepted:
06
02
2020
entrez:
20
2
2020
pubmed:
20
2
2020
medline:
16
3
2021
Statut:
epublish
Résumé
The iron-sulfur (FeS) cluster helicase DDX11 is associated with a human disorder termed Warsaw Breakage Syndrome. Interestingly, one disease-associated mutation affects the highly conserved arginine-263 in the FeS cluster-binding motif. Here, we demonstrate that the FeS cluster in DDX11 is required for DNA binding, ATP hydrolysis, and DNA helicase activity, and that arginine-263 affects FeS cluster binding, most likely because of its positive charge. We further show that DDX11 interacts with the replication factors DNA polymerase delta and WDHD1. In vitro, DDX11 can remove DNA obstacles ahead of Pol δ in an ATPase- and FeS domain-dependent manner, and hence generate single-stranded DNA. Accordingly, depletion of DDX11 causes reduced levels of single-stranded DNA, a reduction of chromatin-bound replication protein A, and impaired CHK1 phosphorylation at serine-345. Taken together, we propose that DDX11 plays a role in dismantling secondary structures during DNA replication, thereby promoting CHK1 activation.
Identifiants
pubmed: 32071282
pii: 3/3/e201900547
doi: 10.26508/lsa.201900547
pmc: PMC7032568
pii:
doi:
Substances chimiques
Cell Cycle Proteins
0
DNA, Single-Stranded
0
DNA-Binding Proteins
0
RPA1 protein, human
0
Replication Protein A
0
WDHD1 protein, human
0
DNA
9007-49-2
CHEK1 protein, human
EC 2.7.11.1
Checkpoint Kinase 1
EC 2.7.11.1
DNA Polymerase III
EC 2.7.7.7
Adenosine Triphosphatases
EC 3.6.1.-
DNA Helicases
EC 3.6.4.-
DDX11 protein, human
EC 3.6.4.13
DEAD-box RNA Helicases
EC 3.6.4.13
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2020 Simon et al.
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