PXD004912

PXD004912 is an original dataset announced via ProteomeXchange.

Title	SCAI promotes DNA double-strand break repair in distinct chromosomal contexts
Description	DNA double-strand breaks (DSBs) are highly cytotoxic DNA lesions, whose accurate repair by non-homologous end-joining (NHEJ) or homologous recombination (HR) is crucial for genome integrity and is strongly influenced by the local chromatin environment. Here, we identify SCAI (Suppressor of Cancer Cell Invasion) as a 53BP1-interacting chromatin-associated protein that promotes the functionality of several DSB repair pathways in mammalian cells. SCAI undergoes prominent enrichment at DSB sites through dual mechanisms involving 53BP1-dependent recruitment to DSB-surrounding chromatin and 53BP1-independent accumulation at resected DSBs. Cells lacking SCAI display reduced DSB repair capacity, hypersensitivity to DSB-inflicting agents and genome instability. We demonstrate that SCAI is a mediator of 53BP1-dependent repair of heterochromatin-associated DSBs, facilitating ATM kinase signaling at DSBs in repressive chromatin environments. Moreover, we establish an important role of SCAI in meiotic recombination, as SCAI deficiency in mice leads to germ cell loss and subfertility associated with impaired retention of the DMC1 recombinase on meiotic chromosomes. Collectively, our findings uncover SCAI as a physiologically important component of both NHEJ- and HR-mediated pathways that potentiates DSB repair efficiency in specific chromatin contexts.
HostingRepository	PRIDE
AnnounceDate	2017-10-24
AnnouncementXML	Submission_2017-10-24_02:19:05.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Mario Oroshi
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	LTQ Orbitrap

Revision	Datetime	Status	ChangeLog Entry
0	2016-09-10 15:32:17	ID requested
1	2016-12-12 13:11:33	announced
⏵ 2	2017-10-24 02:19:06	announced	Updated project metadata.

Hansen RK, Mund A, Poulsen SL, Sandoval M, Klement K, Tsouroula K, Tollenaere MA, R, ä, schle M, Soria R, Offermanns S, Worzfeld T, Grosse R, Brandt DT, Rozell B, Mann M, Cole F, Soutoglou E, Goodarzi AA, Daniel JA, Mailand N, Bekker-Jensen S, SCAI promotes DNA double-strand break repair in distinct chromosomal contexts. Nat Cell Biol, 18(12):1357-1366(2016) [pubmed]

curator keyword: Biological, Biomedical

submitter keyword: APMS, DNA repair

Matthias Mann
contact affiliation	Department of Proteomics and Signal Transduction Max Planck Institute of Biochemistry
contact email	mmann@biochem.mpg.de
lab head
Mario Oroshi
contact affiliation	Proteomics
contact email	oroshi@biochem.mpg.de
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD004912
     1. Label: PRIDE project
     2. Name: SCAI promotes DNA double-strand break repair in distinct chromosomal contexts