Synthetic Lethality between DNA Polymerase Epsilon and RTEL1 in Metazoan DNA Replication.
DNA polymerase epsilon
DNA replication
RTEL1
genome stability
origin activation
Journal
Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691
Informations de publication
Date de publication:
26 05 2020
26 05 2020
Historique:
received:
20
02
2020
revised:
28
03
2020
accepted:
30
04
2020
entrez:
28
5
2020
pubmed:
28
5
2020
medline:
22
5
2021
Statut:
ppublish
Résumé
Genome stability requires coordination of DNA replication origin activation and replication fork progression. RTEL1 is a regulator of homologous recombination (HR) implicated in meiotic cross-over control and DNA repair in C. elegans. Through a genome-wide synthetic lethal screen, we uncovered an essential genetic interaction between RTEL1 and DNA polymerase (Pol) epsilon. Loss of POLE4, an accessory subunit of Pol epsilon, has no overt phenotype in worms. In contrast, the combined loss of POLE-4 and RTEL-1 results in embryonic lethality, accumulation of HR intermediates, genome instability, and cessation of DNA replication. Similarly, loss of Rtel1 in Pole4
Identifiants
pubmed: 32460026
pii: S2211-1247(20)30628-8
doi: 10.1016/j.celrep.2020.107675
pmc: PMC7262601
pii:
doi:
Substances chimiques
DNA Polymerase II
EC 2.7.7.7
RTEL1 protein, human
EC 3.6.1.-
DNA Helicases
EC 3.6.4.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
107675Subventions
Organisme : Cancer Research UK
ID : FC0010048
Pays : United Kingdom
Organisme : Medical Research Council
ID : FC0010048
Pays : United Kingdom
Organisme : Wellcome Trust
ID : FC0010048
Pays : United Kingdom
Informations de copyright
Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Interests S.J.B. is scientific co-founder and SVP Science Strategy at Artios Pharma Ltd., Babraham, UK.
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