PXD006106

PXD006106 is an original dataset announced via ProteomeXchange.

Title	Aldehyde exposure unmasks genome instability in cells heterozygous for clinically relevant BRCA2 mutations
Description	Abnormalities provoked in human cells heterozygous for clinically relevant truncating mutations in BRCA2 by their exposure to naturally occurring aldehydes define a mechanism promoting carcinogenesis in mutation carriers. The ubiquitous metabolite and environmental toxin, formaldehyde, triggers replication fork instability and structural chromosomal aberrations in BRCA2 heterozygous cells. These abnormalities arise from a previously unrecognized effect of formaldehyde to selectively induce the proteasomal degradation of BRCA2, inducing functional haploinsufficiency only in cells where BRCA2 expression is already compromised by a heterozygous mutation. Similar effects are observed with acetaldehyde, a toxic product of alcohol catabolism. Replication fork instability and chromosomal aberrations in aldehyde-exposed cells arise from the unscheduled accumulation of RNA-DNA hybrids, revealing a mechanism driving genomic instability in BRCA2 heterozygous cells. We propose a model for cancer pathogenesis in which aldehyde exposure unmasks the carcinogenic potential of heterozygous BRCA2 mutations, with public health implications in mutation carriers.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_04:04:43.701.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yansheng Liu
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	monohydroxylated residue; iodoacetamide derivatized residue
Instrument	TripleTOF 5600

Revision	Datetime	Status	ChangeLog Entry
0	2017-03-17 04:39:29	ID requested
1	2017-06-01 23:53:22	announced
2	2017-06-06 04:46:56	announced	Updated publication reference for PubMed record(s): 28575672.
⏵ 3	2024-10-22 04:04:51	announced	2024-10-22: Updated project metadata.

10.1016/j.cell.2017.05.010;

Tan SLW, Chadha S, Liu Y, Gabasova E, Perera D, Ahmed K, Constantinou S, Renaudin X, Lee M, Aebersold R, Venkitaraman AR, A Class of Environmental and Endogenous Toxins Induces BRCA2 Haploinsufficiency and Genome Instability. Cell, 169(6):1105-1118.e15(2017) [pubmed]

curator keyword: Biomedical

submitter keyword: Hela, SWATH, Aldehyde

Ruedi Aebersold
contact affiliation	Department of Biology, Institute of Molecular Systems iiology, ETH Zürich, Switzerland
contact email	aebersold@imsb.biol.ethz.ch
lab head
Yansheng Liu
contact affiliation	Institute of Molecular Systems Biology, ETH Zurich
contact email	liu@imsb.biol.ethz.ch
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/2017/06/PXD006106

PRIDE project URI

• PRIDE
  1. PXD006106
     1. Label: PRIDE project
     2. Name: Aldehyde exposure unmasks genome instability in cells heterozygous for clinically relevant BRCA2 mutations