Evidence map›Paper›PMID 39763784›Full record

ArticlebioRxiv : the preprint server for biology2024

Huntingtin interactome reveals huntingtin role in regulation of double strand break DNA damage response (DSB/DDR), chromatin remodeling and RNA processing pathways.

Tamara Ratovitski, Chloe D Holland, Robert N O'Meally, Alexey V Shevelkin, Tianze Shi, Robert N Cole, Mali Jiang, Christopher A Ross

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in bioRxiv : the preprint server for biology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

8 authors.

Tamara RatovitskiDivision of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 North Wolfe Street, CMSC 5 South, Baltimore, MD21287.ORCID 0000-0003-4020-5644
Chloe D HollandDivision of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 North Wolfe Street, CMSC 5 South, Baltimore, MD21287.
Robert N O'MeallyMass Spectrometry and Proteomics Facility, Department of Biological Chemistry, Johns Hopkins University School of Medicine, 733 N. Broadway Street, Suite 371 BRB Baltimore, MD21287.
Alexey V ShevelkinDivision of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 North Wolfe Street, CMSC 5 South, Baltimore, MD21287.
Tianze ShiDivision of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 North Wolfe Street, CMSC 5 South, Baltimore, MD21287.
Robert N ColeMass Spectrometry and Proteomics Facility, Department of Biological Chemistry, Johns Hopkins University School of Medicine, 733 N. Broadway Street, Suite 371 BRB Baltimore, MD21287.
Mali JiangDivision of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 North Wolfe Street, CMSC 5 South, Baltimore, MD21287.
Christopher A RossDivision of Neurobiology, Department of Psychiatry and Behavioral Sciences, Johns Hopkins University School of Medicine, 600 North Wolfe Street, CMSC 5 South, Baltimore, MD21287.

Funding

Targeting Protein Arginine Methylation in HDR21NS109412 · NINDS · JOHNS HOPKINS UNIVERSITY · PI RATOVITSKI, TAMARA · 2019 to 2020
$450k
In vivo efficacy of a kinase inhibitor, roscovitine, in HD mouse modelR21NS125063 · NINDS · JOHNS HOPKINS UNIVERSITY · PI JIN, JING · 2022 to 2022
$450k
NINDS NIH HHS R21 NS109412NINDS NIH HHS R21 NS125063
6 · The paper itself

Abstract

Huntington's Disease (HD), a progressive neurodegenerative disorder with no disease-modifying therapies, is caused by a CAG repeat expansion in the HD gene encoding polyglutamine-expanded huntingtin (HTT) protein. Mechanisms of HD cellular pathogenesis and cellular functions of the normal and mutant HTT proteins are still not completely understood. HTT protein has numerous interaction partners, and it likely provides a scaffold for assembly of multiprotein complexes many of which may be altered in HD. Previous studies have implicated DNA damage response in HD pathogenesis. Gene transcription and RNA processing has also emerged as molecular mechanisms associated with HD. Here we used multiple approaches to identify HTT interactors in the context of DNA damage stress. Our results indicate that HTT interacts with many proteins involved in the regulation of interconnected DNA repair/remodeling and RNA processing pathways. We present evidence for a role for HTT in double strand break repair mechanism. We demonstrate HTT functional interaction with a major DNA damage response kinase DNA-PKcs and association of both proteins with nuclear speckles. We show that S1181 phosphorylation of HTT is regulated by DSB, and can be carried out (at least

Indexed as

DNA damagehuntingtinHuntington’s Diseaseneurodegenerationpost-translational modificationsprotein interactionsRNA processing

Identifiers

PMID39763784
PMCPMC11703178

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.