DICER ribonuclease removes harmful R-loops.

Humans R-Loop Structures / genetics Ribonucleases / genetics RNA / genetics DNA DNA Replication DNA Helicases / genetics Ribonuclease H / genetics Genomic Instability
DICER DICER1 syndrome DNA damage R-loops RNA nuclease genetic instability replication fork stalling

Journal

Molecular cell
ISSN: 1097-4164
Titre abrégé: Mol Cell
Pays: United States
ID NLM: 9802571

Informations de publication

Date de publication:
19 10 2023
Historique:
received: 01 12 2022
revised: 08 07 2023
accepted: 19 09 2023
medline: 27 10 2023
pubmed: 13 10 2023
entrez: 12 10 2023
Statut: ppublish

Résumé

R-loops, which consist of a DNA-RNA hybrid and a displaced DNA strand, are known to threaten genome integrity. To counteract this, different mechanisms suppress R-loop accumulation by either preventing the hybridization of RNA with the DNA template (RNA biogenesis factors), unwinding the hybrid (DNA-RNA helicases), or degrading the RNA moiety of the R-loop (type H ribonucleases [RNases H]). Thus far, RNases H are the only nucleases known to cleave DNA-RNA hybrids. Now, we show that the RNase DICER also resolves R-loops. Biochemical analysis reveals that DICER acts by specifically cleaving the RNA within R-loops. Importantly, a DICER RNase mutant impaired in R-loop processing causes a strong accumulation of R-loops in cells. Our results thus not only reveal a function of DICER as an R-loop resolvase independent of DROSHA but also provide evidence for the role of multi-functional RNA processing factors in the maintenance of genome integrity in higher eukaryotes.

Identifiants

DOI: 10.1016/j.molcel.2023.09.021 PMID: 37827159
pubmed: 37827159
pii: S1097-2765(23)00748-7
doi: 10.1016/j.molcel.2023.09.021
pii:
doi:

Substances chimiques

Ribonucleases EC 3.1.-
RNA 63231-63-0
DNA 9007-49-2
DNA Helicases EC 3.6.4.-
Ribonuclease H EC 3.1.26.4

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

3707-3719.e5

Subventions

Organisme : NIEHS NIH HHS
ID : R01 ES007061
Pays : United States
Organisme : NCI NIH HHS
ID : R01 CA168635
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA241801
Pays : United States

Informations de copyright

Copyright © 2023 Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

Auteurs

Lola P Camino (LP)

Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla, CSIC, 41092 Seville, Spain; Departamento de Genética, Facultad de Biología, Universidad de Sevilla, 41012 Seville, Spain.

Arijit Dutta (A)

Greehey Children's Cancer Research Institute, Department of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.

Sonia Barroso (S)

Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla, CSIC, 41092 Seville, Spain; Departamento de Genética, Facultad de Biología, Universidad de Sevilla, 41012 Seville, Spain.

Carmen Pérez-Calero (C)

Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla, CSIC, 41092 Seville, Spain; Departamento de Genética, Facultad de Biología, Universidad de Sevilla, 41012 Seville, Spain.

Jeffrey N Katz (JN)

Greehey Children's Cancer Research Institute, Department of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA.

María García-Rubio (M)

Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla, CSIC, 41092 Seville, Spain; Departamento de Genética, Facultad de Biología, Universidad de Sevilla, 41012 Seville, Spain.

Patrick Sung (P)

Greehey Children's Cancer Research Institute, Department of Biochemistry and Structural Biology, University of Texas Health Science Center at San Antonio, San Antonio, TX 78229, USA. Electronic address: sungp@uthscsa.edu.

Belén Gómez-González (B)

Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla, CSIC, 41092 Seville, Spain; Departamento de Genética, Facultad de Biología, Universidad de Sevilla, 41012 Seville, Spain. Electronic address: gomezb@us.es.

Andrés Aguilera (A)

Centro Andaluz de Biología Molecular y Medicina Regenerativa-CABIMER, Universidad de Sevilla, CSIC, 41092 Seville, Spain; Departamento de Genética, Facultad de Biología, Universidad de Sevilla, 41012 Seville, Spain. Electronic address: aguilo@us.es.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › DICER ribonuclease removes harmful R-loops.
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Conformation d'acide nucléique › Structures en boucle R › DICER ribonuclease removes harmful R-loops.
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Esterases › Ribonucléases › DICER ribonuclease removes harmful R-loops.
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ARN › DICER ribonuclease removes harmful R-loops.
questionsmedicales.fr › Acides nucléiques, nucléotides et nucléosides › Acides nucléiques › ADN › DICER ribonuclease removes harmful R-loops.
questionsmedicales.fr › Phénomènes génétiques › Réplication de l'ADN › DICER ribonuclease removes harmful R-loops.
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Isomerases › Helicase › DICER ribonuclease removes harmful R-loops.
questionsmedicales.fr › Enzymes et coenzymes › Enzymes › Hydrolases › Esterases › Ribonucléases › Endoribonucleases › Ribonuclease H › DICER ribonuclease removes harmful R-loops.
questionsmedicales.fr › Phénomènes génétiques › Instabilité du génome › DICER ribonuclease removes harmful R-loops.