PXD036905

PXD036905 is an original dataset announced via ProteomeXchange.

Title	SIRT1 regulates DNA damage signaling through PP4 phosphatase complex
Description	The Sirtuin family of NAD+-dependent enzymes play an important role in the maintenance of genome stability upon stress. Several mammalian Sirtuins have been linked directly or indirectly to the regulation of DNA damage during replication through Homologous recombination (HR). The role of one of them, SIRT1, is intriguing as it seems to have a general regulatory role in DNA damage response (DDR) that has not been addressed. SIRT1-deficient cells show impairment of DDR reflected in a decrease in repair capacity, increased genome instability and decreased levels of H2AX. Here we unveil a close functional antagonism between SIRT1 and the PP4 phosphatase multiprotein complex in the regulation of DDR. Upon DNA damage SIRT1 interacts specifically with PP4C and promotes its inhibition through deacetylation of the domain WH1 of the PP4R3/ regulatory subunits. This in turn, regulates H2AX signal and RPA2 phosphorylation, two key events in the signaling of DNA damage and repair by HR. We propose a mechanism whereby during stress SIRT1 signaling ensures a global control of DNA damage through PP4.
HostingRepository	PRIDE
AnnounceDate	2023-11-14
AnnouncementXML	Submission_2023-11-14_09:00:50.534.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Joan Josep Bech-Serra
SpeciesList	scientific name: Mus musculus (Mouse); NCBI TaxID: 10090; scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue
Instrument	LTQ Orbitrap Velos

Revision	Datetime	Status	ChangeLog Entry
0	2022-09-21 14:48:38	ID requested
1	2023-06-15 04:07:53	announced
⏵ 2	2023-11-14 09:00:56	announced	2023-11-14: Updated project metadata.

Rasti G, Becker M, Vazquez BN, Espinosa-Alcantud M, Fern, á, ndez-Duran I, G, á, mez-Garc, í, a A, Ianni A, Gonzalez J, Bosch-Presegu, é L, Marazuela-Duque A, Guitart-Solanes A, Segura-Bayona S, Bech-Serra JJ, Scher M, Serrano L, Shankavaram U, Erdjument-Bromage H, Tempst P, Reinberg D, Olivella M, Stracker TH, de la Torre C, Vaquero A, SIRT1 regulates DNA damage signaling through the PP4 phosphatase complex. Nucleic Acids Res, 51(13):6754-6769(2023) [pubmed]

submitter keyword: label free proteomics,PP4 phosphatase complex, H2AX, SIRT1, DNA damage response

Alex Vaquero
contact affiliation	Chromatin Biology Laboratory, Josep Carreras Leukaemia Research Institute (IJC), Ctra de Can Ruti, Camí de les Escoles s/n, 08916, Badalona, Barcelona, Spain
contact email	avaquero@carrerasresearch.org
lab head
Joan Josep Bech-Serra
contact affiliation	Proteomics Unit - Josep Carreras Leukaemia Research Institute
contact email	jbech@carrerasresearch.org
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD036905
     1. Label: PRIDE project
     2. Name: SIRT1 regulates DNA damage signaling through PP4 phosphatase complex