PXD044158

PXD044158 is an original dataset announced via ProteomeXchange.

Title	Antagonistic roles of canonical and alternative-RPA in disease-associated tandem CAG repeat instability
Description	Ongoing CAG expansions in Spinocerebellar ataxia type 1 (SCA1) and Huntington disease (HD) brains exacerbate disease.  Expansions involve aberrant repair of mutagenic slipped-DNAs, formed from single-stranded DNAs.  Whether single stranded DNA-binding proteins prevent or facilitate expansions is unknown.  We assessed canonical RPA (RPA1-RPA2-RPA3) and Alternative-RPA (RPA1-RPA4- RPA3), containing primate-specific RPA4.  RPA is essential for all DNA metabolism.  Alt-RPA has undefined functions.  Alt-RPA is upregulated 10-fold in HD and SCA1 patient brains.  RPA enhances, while Alt-RPA blocks, correct repair of slipped-CAGs.  RPA, but not Alt-RPA, efficiently binds and melts slipped-DNAs.  RPA enhances, while Alt-RPA blocks, removal of excess slipped-DNAs by FAN1 nuclease.  Protein-protein interactomes reveal unique and shared partners of RPA and Alt-RPA, including expansion-driving proteins.  RPA-overexpression in SCA1 mice inhibits CAG expansions in brains, rescuing neuron morphology and motor phenotypes.  Modulating repeat mutations is one example involving antagonistic Alt-RPA↔RPA interactions, illuminating questions as to which RPA-mediated processes are also modulated by Alt RPA.
HostingRepository	PRIDE
AnnounceDate	2023-10-14
AnnouncementXML	Submission_2023-10-17_03:17:28.073.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	JenniferRaisch
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	carbamoylated residue; acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	autoflex

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-27 15:59:59	ID requested
⏵ 1	2023-10-17 03:17:28	announced

ProteomeXchange project tag: Biology/Disease-Driven Human Proteome Project (B/D-HPP), Human Proteome Project

submitter keyword: CAG repeat expansion diseases

Spinocerebellar Ataxia type 1 (SCA1)

Huntington's disease (HD)

somatic CAG repeat expansions

RPA (single-strand DNA binding protein

Alternative-RPA (Alt-RPA)

DNA repair, slipped-DNAs

post-mortem brains, SCA1 mice

Francois-MichelBoisvert
contact affiliation	Sherbrooke University, Immunology and cellular biology department, FMSS
contact email	francois.michel.boisvert@usherbrooke.ca
lab head
JenniferRaisch
contact affiliation	Sherbrooke Universitty
contact email	jennifer.raisch@usherbrooke.ca
dataset submitter

Dataset FTP location NOTE: Most web browsers have now discontinued native support for FTP access within the browser window. But you can usually install another FTP app (we recommend FileZilla) and configure your browser to launch the external application when you click on this FTP link. Or otherwise, launch an app that supports FTP (like FileZilla) and use this address: ftp://ftp.pride.ebi.ac.uk/pride/data/archive/2023/10/PXD044158

PRIDE project URI

• PRIDE
  1. PXD044158
     1. Label: PRIDE project
     2. Name: Antagonistic roles of canonical and alternative-RPA in disease-associated tandem CAG repeat instability