PXD035943

PXD035943 is an original dataset announced via ProteomeXchange.

Title	RAD51AP1 regulates ALT-HDR through chromatin-directed homeostasis of TERRA
Description	Alternative lengthening of telomeres (ALT) is a homology-directed repair (HDR) mechanism of telomere elongation that controls proliferation in subsets of highly aggressive cancer. Recent studies have revealed that TERRA (telomere repeat-containing RNA) acts to initiate ALT-associated HDR (ALT-HDR). Here we report that RAD51AP1, a crucial ALT factor, interacts with TERRA and utilizes it to generate D- and R- loop HR intermediates. We also show that RAD51AP1 binds to and may generate and potentially stabilize TERRA-containing R-loops as RAD51AP1 depletion reduces R-loop formation at telomere DNA breaks. Proteomic analyses uncover a new role for RAD51AP1 mediated TERRA R-loop homeostasis in a mechanism of chromatin-directed suppression of TERRA and prevention of transcription-replication collisions during ALT-HDR. Intriguingly, we find that both TERRA binding and this non-canonical function of RAD51AP1 require its intrinsic SUMO-SIM regulatory axis. These findings provide new insights into the multi-contextual functions of RAD51AP1 within the ALT mechanism and regulation of TERRA.
HostingRepository	PRIDE
AnnounceDate	2024-01-26
AnnouncementXML	Submission_2024-01-26_06:50:49.096.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alexey Nesvizhskii
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2022-08-10 09:20:11	ID requested
⏵ 1	2024-01-26 06:50:50	announced

10.1016/j.molcel.2022.09.025;

Kaminski N, Wondisford AR, Kwon Y, Lynskey ML, Bhargava R, Barroso-Gonz, á, lez J, Garc, í, a-Exp, ó, sito L, He B, Xu M, Mellacheruvu D, Watkins SC, Modesti M, Miller KM, Nesvizhskii AI, Zhang H, Sung P, O'Sullivan RJ, RAD51AP1 regulates ALT-HDR through chromatin-directed homeostasis of TERRA. Mol Cell, 82(21):4001-4017.e7(2022) [pubmed]

submitter keyword: Cancer,ALT, TERRA, Homology-Directed Repair, Chromatin, Transcription, Telomere, RAD51AP1

Roderick J O'Sullivan
contact affiliation	Dept.Pharmacology & Chemical Biology UPMC Hillman Cancer Center
contact email	osullivanr@upmc.edu
lab head
Alexey Nesvizhskii
contact affiliation	University of Michigan, Ann Arbor
contact email	nesvi@med.umich.edu
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/2024/01/PXD035943

PRIDE project URI

• PRIDE
  1. PXD035943
     1. Label: PRIDE project
     2. Name: RAD51AP1 regulates ALT-HDR through chromatin-directed homeostasis of TERRA