Expression of human RECQL5 in Saccharomyces cerevisiae causes transcription defects and transcription-associated genome instability.
Genome instability
RECQL5 helicase
Recombination
Transcription
Journal
Molecular genetics and genomics : MGG
ISSN: 1617-4623
Titre abrégé: Mol Genet Genomics
Pays: Germany
ID NLM: 101093320
Informations de publication
Date de publication:
26 May 2024
26 May 2024
Historique:
received:
21
11
2023
accepted:
13
05
2024
medline:
26
5
2024
pubmed:
26
5
2024
entrez:
26
5
2024
Statut:
epublish
Résumé
RECQL5 is a member of the conserved RecQ family of DNA helicases involved in the maintenance of genome stability that is specifically found in higher eukaryotes and associates with the elongating RNA polymerase II. To expand our understanding of its function we expressed human RECQL5 in the yeast Saccharomyces cerevisiae, which does not have a RECQL5 ortholog. We found that RECQL5 expression leads to cell growth inhibition, increased genotoxic sensitivity and transcription-associated hyperrecombination. Chromatin immunoprecipitation and transcriptomic analysis of yeast cells expressing human RECQL5 shows that this is recruited to transcribed genes and although it causes only a weak impact on gene expression, in particular at G + C-rich genes, it leads to a transcription termination defect detected as readthrough transcription. The data indicate that the interaction between RNAPII and RECQL5 is conserved from yeast to humans. Unexpectedly, however, the RECQL5-ID mutant, previously shown to have reduced the association with RNAPII in vitro, associates with the transcribing polymerase in cells. As a result, expression of RECQL5-ID leads to similar although weaker phenotypes than wild-type RECQL5 that could be transcription-mediated. Altogether, the data suggests that RECQL5 has the intrinsic ability to function in transcription-dependent and independent genome dynamics in S. cerevisiae.
Identifiants
pubmed: 38796829
doi: 10.1007/s00438-024-02152-3
pii: 10.1007/s00438-024-02152-3
doi:
Substances chimiques
RecQ Helicases
EC 3.6.4.12
RECQL5 protein, human
0
RNA Polymerase II
EC 2.7.7.-
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
59Subventions
Organisme : Ministry of Science and Innovation-Spain
ID : BFU2016-75058-P
Organisme : European Research Council
ID : ERC2014 AdG669898 TARLOOP
Pays : International
Organisme : European Research Council
ID : Agreement 693327
Pays : International
Organisme : Laureate grant from the Novo Nordisk Foundation
ID : NNF19OC0055875
Organisme : Chair grant from the Danish National Research Foundation
ID : DNRF153
Organisme : Instituto de Salud Carlos III-Ministry of Science and Innovation Spain.
ID : PFIS. FI10/00332
Informations de copyright
© 2024. The Author(s).
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