ARGLU1 enhances promoter-proximal pausing of RNA polymerase II and stimulates DNA damage repair.

Autor:	Bachus S; Department of Microbiology, University of Manitoba, 45 Chancellor's Circle, Buller Building Room 427, Winnipeg, MB R3T 2N2, Canada., Akkerman N; Department of Microbiology, University of Manitoba, 45 Chancellor's Circle, Buller Building Room 427, Winnipeg, MB R3T 2N2, Canada., Fulham L; Department of Microbiology, University of Manitoba, 45 Chancellor's Circle, Buller Building Room 427, Winnipeg, MB R3T 2N2, Canada., Graves D; Department of Microbiology, University of Manitoba, 45 Chancellor's Circle, Buller Building Room 427, Winnipeg, MB R3T 2N2, Canada., Helwer R; Department of Microbiology, University of Manitoba, 45 Chancellor's Circle, Buller Building Room 427, Winnipeg, MB R3T 2N2, Canada., Rempel J; Department of Microbiology, University of Manitoba, 45 Chancellor's Circle, Buller Building Room 427, Winnipeg, MB R3T 2N2, Canada., Pelka P; Department of Microbiology, University of Manitoba, 45 Chancellor's Circle, Buller Building Room 427, Winnipeg, MB R3T 2N2, Canada.; Department of Medical Microbiology and Infectious Diseases, University of Manitoba, 45 Chancellor's Circle, Buller Building Room 427, Winnipeg, MB R3T 2N2, Canada.
Jazyk:	angličtina
Zdroj:	Nucleic acids research [Nucleic Acids Res] 2024 Jun 10; Vol. 52 (10), pp. 5658-5675.
DOI:	10.1093/nar/gkae208
Abstrakt:	Arginine and glutamate rich 1 (ARGLU1) is a poorly understood cellular protein with functions in RNA splicing and transcription. Computational prediction suggests that ARGLU1 contains intrinsically disordered regions and lacks any known structural or functional domains. We used adenovirus Early protein 1A (E1A) to probe for critical regulators of important cellular pathways and identified ARGLU1 as a significant player in transcription and the DNA damage response pathway. Transcriptional effects induced by ARGLU1 occur via enhancement of promoter-proximal RNA polymerase II pausing, likely by inhibiting the interaction between JMJD6 and BRD4. When overexpressed, ARGLU1 increases the growth rate of cancer cells, while its knockdown leads to growth arrest. Significantly, overexpression of ARGLU1 increased cancer cell resistance to genotoxic drugs and promoted DNA damage repair. These results identify new roles for ARGLU1 in cancer cell survival and the DNA damage repair pathway, with potential clinical implications for chemotherapy resistance. (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)
Databáze:	MEDLINE
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