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- W3088135499 abstract "ABSTRACT Transcription restart after a genotoxic challenge is a fundamental yet poorly understood process. Here, we dissect the interplay between transcription and chromatin restoration after DNA damage by focusing on the human histone chaperone complex HIRA, which is required for transcription recovery post UV. We demonstrate that HIRA is recruited to UV-damaged chromatin via the ubiquitin-dependent segregase VCP to deposit new H3.3 histones. However, this local activity of HIRA is dispensable for transcription recovery. Instead, we reveal a genome-wide function of HIRA in transcription restart that is independent of new H3.3 and not restricted to UV-damaged loci. HIRA coordinates with ASF1B to control transcription restart by two independent pathways: by stabilizing the associated subunit UBN2 and by reducing the expression of the transcription repressor ATF3. Thus, HIRA primes UV-damaged chromatin for transcription restart at least in part by relieving transcription inhibition rather than by depositing new H3.3 as an activating bookmark." @default.
- W3088135499 created "2020-10-01" @default.
- W3088135499 creator A5037194300 @default.
- W3088135499 creator A5038882155 @default.
- W3088135499 creator A5048423328 @default.
- W3088135499 creator A5052545112 @default.
- W3088135499 creator A5052790050 @default.
- W3088135499 creator A5065179640 @default.
- W3088135499 date "2020-09-25" @default.
- W3088135499 modified "2023-09-30" @default.
- W3088135499 title "Dissecting regulatory pathways for transcription recovery following DNA damage reveals a non-canonical function of the histone chaperone HIRA" @default.
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- W3088135499 doi "https://doi.org/10.1101/2020.09.25.313130" @default.