Molecular underpinnings and environmental drivers of loss of heterozygosity in Drosophila intestinal stem cells.

CP: Developmental biology CP: Genomics

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
29 Nov 2023
Historique:
received: 03 08 2022
revised: 29 09 2023
accepted: 08 11 2023
medline: 30 11 2023
pubmed: 30 11 2023
entrez: 30 11 2023
Statut: aheadofprint

Résumé

During development and aging, genome mutation leading to loss of heterozygosity (LOH) can uncover recessive phenotypes within tissue compartments. This phenomenon occurs in normal human tissues and is prevalent in pathological genetic conditions and cancers. While studies in yeast have defined DNA repair mechanisms that can promote LOH, the predominant pathways and environmental triggers in somatic tissues of multicellular organisms are not well understood. Here, we investigate mechanisms underlying LOH in intestinal stem cells in Drosophila. Infection with the pathogenic bacteria, Erwinia carotovora carotovora 15, but not Pseudomonas entomophila, increases LOH frequency. Using whole genome sequencing of somatic LOH events, we demonstrate that they arise primarily via mitotic recombination. Molecular features and genetic evidence argue against a break-induced replication mechanism and instead support cross-over via double Holliday junction-based repair. This study provides a mechanistic understanding of mitotic recombination, an important mediator of LOH, and its effects on stem cells in vivo.

Identifiants

DOI: 10.1016/j.celrep.2023.113485 PMID: 38032794
pubmed: 38032794
pii: S2211-1247(23)01497-3
doi: 10.1016/j.celrep.2023.113485
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

113485

Informations de copyright

Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

Auteurs

Lara Al Zouabi (L)

Genetics and Developmental Biology Department, Institut Curie, PSL Research University, Sorbonne University, CNRS UMR 3215, INSERM U934, 75248 Paris, France.

Marine Stefanutti (M)

Genetics and Developmental Biology Department, Institut Curie, PSL Research University, Sorbonne University, CNRS UMR 3215, INSERM U934, 75248 Paris, France.

Spyridon Roumeliotis (S)

Genetics and Developmental Biology Department, Institut Curie, PSL Research University, Sorbonne University, CNRS UMR 3215, INSERM U934, 75248 Paris, France.

Gwenn Le Meur (G)

Genetics and Developmental Biology Department, Institut Curie, PSL Research University, Sorbonne University, CNRS UMR 3215, INSERM U934, 75248 Paris, France.

Benjamin Boumard (B)

Genetics and Developmental Biology Department, Institut Curie, PSL Research University, Sorbonne University, CNRS UMR 3215, INSERM U934, 75248 Paris, France.

Nick Riddiford (N)

Genetics and Developmental Biology Department, Institut Curie, PSL Research University, Sorbonne University, CNRS UMR 3215, INSERM U934, 75248 Paris, France.

Natalia Rubanova (N)

Genetics and Developmental Biology Department, Institut Curie, PSL Research University, Sorbonne University, CNRS UMR 3215, INSERM U934, 75248 Paris, France; Bioinformatics, Biostatistics, Epidemiology and Computational Systems Unit, Institut Curie, PSL Research University, INSERM U900, 75005 Paris, France.

Mylène Bohec (M)

ICGex Next-Generation Sequencing Platform, Institut Curie, PSL Research University, 75005 Paris, France.

Louis Gervais (L)

Genetics and Developmental Biology Department, Institut Curie, PSL Research University, Sorbonne University, CNRS UMR 3215, INSERM U934, 75248 Paris, France.

Nicolas Servant (N)

Bioinformatics, Biostatistics, Epidemiology and Computational Systems Unit, Institut Curie, PSL Research University, INSERM U900, 75005 Paris, France.

Allison J Bardin (AJ)

Genetics and Developmental Biology Department, Institut Curie, PSL Research University, Sorbonne University, CNRS UMR 3215, INSERM U934, 75248 Paris, France. Electronic address: allison.bardin@curie.fr.

Classifications MeSH