PXD031357

PXD031357 is an original dataset announced via ProteomeXchange.

Title	SAMHD1 deacetylation by SIRT1 promotes DNA end resection by facilitating DNA binding at double-strand breaks
Description	Sterile alpha motif and HD domain-containing protein 1 (SAMHD1) has a dNTPase-independent function in promoting DNA end resection to facilitate DNA double-strand break (DSB) repair by homologous recombination (HR); however, it is not known if upstream signaling events govern this activity. Here, we show that SAMHD1 is deacetylated by the SIRT1 sirtuin deacetylase, facilitating its binding with ssDNA at DSBs, to promote DNA end resection and HR. SIRT1 complexes with and deacetylates SAMHD1 at conserved lysine 354 (K354) specifically in response to DSBs. K354 deacetylation by SIRT1 promotes DNA end resection and HR but not SAMHD1 tetramerization or dNTPase activity. Mechanistically, K354 deacetylation by SIRT1 promotes SAMHD1 recruitment to DSBs and binding to ssDNA at DSBs, which in turn facilitates CtIP ssDNA binding, leading to promotion of genome integrity. Our findings define a mechanism governing the dNTPase-independent resection function of SAMHD1 by SIRT1 deacetylation in promoting HR and genome stability.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_08:40:23.759.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Duc Duong
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; acetylated residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2022-01-31 01:15:16	ID requested
1	2023-03-11 02:08:58	announced
⏵ 2	2023-11-14 08:40:26	announced	2023-11-14: Updated project metadata.

Kapoor-Vazirani P, Rath SK, Liu X, Shu Z, Bowen NE, Chen Y, Haji-Seyed-Javadi R, Daddacha W, Minten EV, Danelia D, Farchi D, Duong DM, Seyfried NT, Deng X, Ortlund EA, Kim B, Yu DS, SAMHD1 deacetylation by SIRT1 promotes DNA end resection by facilitating DNA binding at double-strand breaks. Nat Commun, 13(1):6707(2022) [pubmed]

submitter keyword: acetylation,IPMS

David Yu
contact affiliation	Department of Radiation Oncology Associate Professor
contact email	dsyu@emory.edu
lab head
Duc Duong
contact affiliation	Center of Neurodegenerative Diseases
contact email	dduong@emory.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/2023/03/PXD031357

PRIDE project URI

• PRIDE
  1. PXD031357
     1. Label: PRIDE project
     2. Name: SAMHD1 deacetylation by SIRT1 promotes DNA end resection by facilitating DNA binding at double-strand breaks