PXD003542

PXD003542 is an original dataset announced via ProteomeXchange.

Title	Proteomic and cellular responses against mutagenesis
Description	Endogenous stress represents a major source of genome instability, but is in essence difficult to apprehend. Incorporation of labeled radionuclides into DNA constitutes a tractable model to analyze cellular responses to endogenous attacks. Here we show that incorporation of [3H]thymidine into CHO hamster cells generates oxidative-induced mutagenesis, but, with a peak at low doses. Proteomic analysis showed that the cellular global response differs between low and high levels of endogenous stress. In particular, these results confirmed the involvement of proteins implicated in redox homeostasis and DNA damage signaling pathways. Induced-mutagenesis was abolished by the anti-oxidant N-acetyl cysteine and plateaued, at high doses, upon exposure to L-buthionine sulfoximine, which represses cellular detoxification. The [3H]thymidine-induced mutation spectrum revealed mostly base substitutions, exhibiting a signature specific for low doses (GC>CG and AT>CG). Consistently, the enzymatic activity of the base excision repair protein APE-1 is induced at only medium or high doses. Collectively, the data reveal that a threshold of endogenous stress must be reached to trigger cellular detoxification and DNA repair programs; below this threshold, the consequences of endogenous stress escape cellular surveillance, leading to high levels of mutagenesis. Therefore, low doses of endogenous local stress can jeopardize genome integrity more efficiently than higher doses.
HostingRepository	PRIDE
AnnounceDate	2016-07-15
AnnouncementXML	Submission_2016-07-15_03:24:12.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD003542
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	sonia hem
SpeciesList	scientific name: Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus); NCBI TaxID: 10029;
ModificationList	Oxidation; Carbamidomethyl
Instrument	maXis

Revision	Datetime	Status	ChangeLog Entry
0	2016-01-28 02:09:42	ID requested
⏵ 1	2016-07-15 03:24:14	announced

Saintigny Y, Chevalier F, Bravard A, Dardillac E, Laurent D, Hem S, D, é, pagne J, Radicella JP, Lopez BS, A threshold of endogenous stress is required to engage cellular response to protect against mutagenesis. Sci Rep, 6():29412(2016) [pubmed]

curator keyword: Biological

submitter keyword: mutagenesis, proteomic, low doses, endogenous stress, tritium, oxidative stress

Bernard S. Lopez
contact affiliation	UMR CNRS 8200, Institut Gustave Roussy, Université Paris-Saclay, Villejuif, France
contact email	Bernard.LOPEZ@gustaveroussy.fr
lab head
sonia hem
contact affiliation	INRA
contact email	sonia.hem@supagro.inra.fr
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD003542
     1. Label: PRIDE project
     2. Name: Proteomic and cellular responses against mutagenesis