PXD044180-1

PXD044180 is an original dataset announced via ProteomeXchange.

Title	FAM111A regulates replication origin activation and cell fitness
Description	FAM111A is a replisome associated protein and dominant mutations within its trypsin-like peptidase domain are linked to severe human developmental syndrome, the Kenny-Caffey syndrome. However, FAM111A functions remain unclear. Here, we show that FAM111A facilitates efficient activation of DNA replication origins. Upon replication fork stalling, FAM111A promotes dormant origin activation and ssDNA exposure. Furthermore, unrestrained expression of FAM111A wild-type as well as patient mutants causes accumulation of DNA damage and cell death, only when the peptidase domain remains intact. The peptidase domain is responsible for ssDNA exposure during S phase, which is not caused by caspase dependent apoptosis. Altogether, these data unveil how FAM111A promotes DNA replication in normal conditions and becomes harmful in a disease context.
HostingRepository	PRIDE
AnnounceDate	2023-10-03
AnnouncementXML	Submission_2023-10-03_00:29:53.179.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	ConstanceAlabert
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	phosphorylated residue; monohydroxylated residue; iodoacetamide derivatized residue
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2023-07-28 06:05:37	ID requested
⏵ 1	2023-10-03 00:29:53	announced
2	2024-10-22 06:04:40	announced	2024-10-22: Updated project metadata.

Dataset with its publication pending

submitter keyword: DNA replication, developmental syndrome, peptidase, genome stability

ConstanceAlabert
contact affiliation	Molecular Cell and Developmental Biology, School of Life Sciences, University of Dundee
contact email	c.alabert@dundee.ac.uk
lab head
ConstanceAlabert
contact affiliation	University of Dundee
contact email	calabert@dundee.ac.uk
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD044180
     1. Label: PRIDE project
     2. Name: FAM111A regulates replication origin activation and cell fitness