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PXD019156

PXD019156 is an original dataset announced via ProteomeXchange.

Dataset Summary
TitleMCM8IP activates the MCM8-9 helicase to promote DNA synthesis and homologous recombination upon DNA damage
DescriptionHomologous recombination (HR) mediates the error-free repair of DNA double-strand breaks to maintain genomic stability. Here we characterize C17orf53/MCM8IP, an OB-fold containing protein that binds ssDNA, as a DNA repair factor involved in HR. MCM8IP-deficient cells exhibit HR defects, especially in long-tract gene conversion, occurring downstream of RAD51 loading, consistent with a role for MCM8IP in HR-dependent DNA synthesis. Moreover, loss of MCM8IP confers cellular sensitivity to crosslinking agents and PARP inhibition. Importantly, we report that MCM8IP directly associates with MCM8-9, a helicase complex mutated in primary ovarian insufficiency, and RPA1. We additionally show that the interactions of MCM8IP with MCM8-9 and RPA facilitate HR and promote replication fork progression and cellular viability in response to treatment with crosslinking agents. Mechanistically, MCM8IP stimulates the helicase activity of MCM8-9. Collectively, our work identifies MCM8IP as a key regulator of DNA damage-associated DNA synthesis during DNA recombination and replication.
HostingRepositoryPRIDE
AnnounceDate2020-06-15
AnnouncementXMLSubmission_2020-06-15_02:50:45.xml
DigitalObjectIdentifier
ReviewLevelPeer-reviewed dataset
DatasetOriginOriginal dataset
RepositorySupportUnsupported dataset by repository
PrimarySubmitterAlberto Ciccia
SpeciesList scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationListNo PTMs are included in the dataset
InstrumentQ Exactive HF; Orbitrap Fusion
Dataset History
RevisionDatetimeStatusChangeLog Entry
02020-05-12 22:53:00ID requested
12020-06-15 02:50:46announced
Publication List
Huang JW, Acharya A, Taglialatela A, Nambiar TS, Cuella-Martin R, Leuzzi G, Hayward SB, Joseph SA, Brunette GJ, Anand R, Soni RK, Clark NL, Bernstein KA, Cejka P, Ciccia A, MCM8IP activates the MCM8-9 helicase to promote DNA synthesis and homologous recombination upon DNA damage. Nat Commun, 11(1):2948(2020) [pubmed]
Keyword List
submitter keyword: C17orf53, MCM8IP, RPA, MCM8, MCM9, Homologous recombination, cisplatin
Contact List
Alberto Ciccia
contact affiliationDepartment of Genetics and Development Herbert Irving Comprehensive Cancer Center Columbia University Irving Medical Center New York, NY, USA
contact emailac3685@cumc.columbia.edu
lab head
Alberto Ciccia
contact affiliationColumbia University Irving Medical Center
contact emailac3685@cumc.columbia.edu
dataset submitter
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