PXD005690

PXD005690 is an original dataset announced via ProteomeXchange.

Title	DONSON encodes a novel replication fork protection factor mutated in 2 microcephalic dwarfism.
Description	To ensure efficient genome duplication, cells have evolved a multitude of factors that promote unperturbed DNA replication, and protect, repair and restart damaged forks. Here we identify DONSON as a novel fork protection factor, and report biallelic DONSON mutations in individuals with microcephalic dwarfism. We demonstrate that DONSON is a component of the replisome that stabilises forks during normal genome replication. Loss of DONSON leads to severe replication-associated DNA damage arising from nucleolytic cleavage of stalled replication forks. Furthermore, ATR-dependent ,signalling in response to replication stress is impaired in DONSON-deficient cells, resulting in decreased checkpoint activity, and potentiating chromosomal instability. Hypomorphic mutations substantially reduce DONSON protein levels and impair fork stability in patient cells, consistent with defective DNA replication underlying the disease phenotype In summary, we identify mutations in DONSON as a common cause of microcephalic dwarfism, and establish DONSON as a critical replication fork protein required for mammalian DNA replication and genome stability
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:35:16.150.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Alex von kriegsheim
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	No PTMs are included in the dataset
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2017-01-12 01:22:01	ID requested
1	2017-02-10 02:52:15	announced
⏵ 2	2024-10-22 04:35:16	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

curator keyword: Biomedical

submitter keyword: interaction proteomics

alex von kriegsheim
contact affiliation	university of edinburgh
contact email	alex.vonkriegsheim@igmm.ed.ac.uk
lab head
Alex von kriegsheim
contact affiliation	University of Edinburgh
contact email	alex.vonkriegsheim@ucd.ie
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD005690
     1. Label: PRIDE project
     2. Name: DONSON encodes a novel replication fork protection factor mutated in 2 microcephalic dwarfism.