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Senataxin, Defective in the Neurodegenerative Disorder Ataxia with Oculomotor Apraxia 2, Lies at the Interface of Transcription and the DNA Damage Response

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Yüce, Özlem, West, Stephen C.·2013·Molecular and Cellular Biology

Abstract

The neurodegenerative disorder ataxia with oculomotor apraxia 2 (AOA-2) is caused by defects in senataxin, a putative RNA/DNA helicase thought to be involved in the termination of transcription at RNA polymerase pause sites. RNA/DNA hybrids (R loops) that arise during transcription pausing lead to genome instability unless they are resolved efficiently. We found that senataxin forms distinct nuclear foci in S/G(2)-phase human cells and that the number of these foci increases in response to impaired DNA replication or DNA damage. Senataxin colocalizes with 53BP1, a key DNA damage response protein, and with other factors involved in DNA repair. Inhibition of transcription using α-amanitin, or the dissolution of R loops by transient expression of RNase H1, leads to the loss of senataxin foci. These results indicate that senataxin localizes to sites of collision between components of the replisome and the transcription apparatus and that it is targeted to R loops, where it plays an important role at the interface of transcription and the DNA damage response.

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Metadata

Authors
Yüce, Ö., & West, S. C.
Venue
Molecular and Cellular Biology
Published
2013-01-01
Volume
33
Issue
2
Pages
406-417
ISSN
  • 0270-7306 (ISSN-L)
  • 1098-5549
OpenAlex
W2120588059
Cited by
191
References
5
FWCI
5.69
Type
journal article
Language
en
Open access
bronze

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CoChat. (2026). Citation check: Senataxin, Defective in the Neurodegenerative Disorder Ataxia with Oculomotor Apraxia 2, Lies at the Interface of Transcription and the DNA Damage Response. https://app.cochat.ai/papers/10.1128/mcb.01195-12
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Yüce, Ö., & West, S. C. (2013). Senataxin, Defective in the Neurodegenerative Disorder Ataxia with Oculomotor Apraxia 2, Lies at the Interface of Transcription and the DNA Damage Response. Molecular and Cellular Biology. https://doi.org/10.1128/mcb.01195-12

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