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Genome Instability and Transcription Elongation Impairment in Human Cells Depleted of THO/TREX

Open access
Domínguez-Sánchez, María S., Barroso, Sonia, Gómez-González, Belén, Luna, Rosa, Aguilera, Andrés·2011·PLoS Genetics

Abstract

THO/TREX connects transcription with genome integrity in yeast, but a role of mammalian THO in these processes is uncertain, which suggests a differential implication of mRNP biogenesis factors in genome integrity in yeast and humans. We show that human THO depletion impairs transcription elongation and mRNA export and increases instability associated with DNA breaks, leading to hyper-recombination and γH2AX and 53BP1 foci accumulation. This is accompanied by replication alteration as determined by DNA combing. Genome instability is R-loop-dependent, as deduced from the ability of the AID enzyme to increase DNA damage and of RNaseH to reduce it, or from the enhancement of R-loop-dependent class-switching caused by THOC1-depletion in CH12 murine cells. Therefore, mammalian THO prevents R-loop formation and has a role in genome dynamics and function consistent with an evolutionary conservation of the functional connection between these mRNP biogenesis factors and genome integrity that had not been anticipated.

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Metadata

Authors
Domínguez-Sánchez, M. S., Barroso, S., Gómez-González, B., Luna, R., & Aguilera, A.
Venue
PLoS Genetics
Published
2011-12-01
Volume
7
Issue
12
Pages
e1002386
ISSN
  • 1553-7390 (ISSN-L)
  • 1553-7404
OpenAlex
W2059453176
Cited by
238
References
1
FWCI
5.64
Type
journal article
Language
en
Open access
gold

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CoChat. (2026). Citation check: Genome Instability and Transcription Elongation Impairment in Human Cells Depleted of THO/TREX. https://app.cochat.ai/papers/10.1371/journal.pgen.1002386
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Domínguez-Sánchez, M. S., Barroso, S., Gómez-González, B., Luna, R., & Aguilera, A. (2011). Genome Instability and Transcription Elongation Impairment in Human Cells Depleted of THO/TREX. PLoS Genetics. https://doi.org/10.1371/journal.pgen.1002386

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