PXD019156-1

PXD019156 is an original dataset announced via ProteomeXchange.

Title	MCM8IP activates the MCM8-9 helicase to promote DNA synthesis and homologous recombination upon DNA damage
Description	Homologous 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.
HostingRepository	PRIDE
AnnounceDate	2020-06-15
AnnouncementXML	Submission_2020-06-15_02:50:45.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alberto Ciccia
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive HF; Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2020-05-12 22:53:00	ID requested
⏵ 1	2020-06-15 02:50:46	announced

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]

submitter keyword: C17orf53, MCM8IP, RPA, MCM8, MCM9, Homologous recombination, cisplatin

Alberto Ciccia
contact affiliation	Department of Genetics and Development Herbert Irving Comprehensive Cancer Center Columbia University Irving Medical Center New York, NY, USA
contact email	ac3685@cumc.columbia.edu
lab head
Alberto Ciccia
contact affiliation	Columbia University Irving Medical Center
contact email	ac3685@cumc.columbia.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/2020/06/PXD019156

PRIDE project URI

• PRIDE
  1. PXD019156
     1. Label: PRIDE project
     2. Name: MCM8IP activates the MCM8-9 helicase to promote DNA synthesis and homologous recombination upon DNA damage