Extended DNA threading through a dual-engine motor module of the activating signal co-integrator 1 complex.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
05 04 2023
05 04 2023
Historique:
received:
28
08
2022
accepted:
21
03
2023
medline:
7
4
2023
entrez:
5
4
2023
pubmed:
6
4
2023
Statut:
epublish
Résumé
Activating signal co-integrator 1 complex (ASCC) subunit 3 (ASCC3) supports diverse genome maintenance and gene expression processes, and contains tandem Ski2-like NTPase/helicase cassettes crucial for these functions. Presently, the molecular mechanisms underlying ASCC3 helicase activity and regulation remain unresolved. We present cryogenic electron microscopy, DNA-protein cross-linking/mass spectrometry as well as in vitro and cellular functional analyses of the ASCC3-TRIP4 sub-module of ASCC. Unlike the related spliceosomal SNRNP200 RNA helicase, ASCC3 can thread substrates through both helicase cassettes. TRIP4 docks on ASCC3 via a zinc finger domain and stimulates the helicase by positioning an ASC-1 homology domain next to the C-terminal helicase cassette of ASCC3, likely supporting substrate engagement and assisting the DNA exit. TRIP4 binds ASCC3 mutually exclusively with the DNA/RNA dealkylase, ALKBH3, directing ASCC3 for specific processes. Our findings define ASCC3-TRIP4 as a tunable motor module of ASCC that encompasses two cooperating NTPase/helicase units functionally expanded by TRIP4.
Identifiants
pubmed: 37019967
doi: 10.1038/s41467-023-37528-3
pii: 10.1038/s41467-023-37528-3
pmc: PMC10076317
doi:
Substances chimiques
Nucleoside-Triphosphatase
EC 3.6.1.15
DNA Helicases
EC 3.6.4.-
RNA Helicases
EC 3.6.4.13
DNA
9007-49-2
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
Pagination
1886Subventions
Organisme : NCI NIH HHS
ID : P01 CA092584
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA193318
Pays : United States
Informations de copyright
© 2023. The Author(s).
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