PXD022351 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | Inhibition of tryptophan 2,3-dioxygenase impairs DNA damage tolerance and repair in glioma cells |
Description | Expression of tryptophan 2,3-dioxygenase (TDO) is a determinant of malignancy in gliomas through kynurenine (KYN) signaling. We report that inhibition of TDO activity attenuated recovery from replication stress and increased the genotoxic effects of bis-chloroethylnitrosourea (BCNU). Activation of the Chk1 arm of the replication stress response (RSR) was reduced when TDO activity was blocked prior to BCNU treatment, whereas phosphorylation of serine 33 (pS33) on replication protein A (RPA) was enhanced - indicative of increased fork collapse. Analysis of quantitative proteomic results revealed TDO-dependent changes in several pathways - including down-regulation of 53BP1 and sirtuin signaling. We went on to show that cells lacking TDO activity exhibited defective recruitment of 53BP1 to gamma-H2AX foci, which corresponded with delayed repair of DNA breaks. Addition of exogenous KYN increased the rate of break repair. TDO inhibition diminished SIRT7 deacetylase recruitment to chromatin, which increased histone H3K18 acetylation - a key mark involved in preventing 53BP1 recruitment to sites of DNA damage. These results highlight the potential for tumor-specific metabolic changes to influence genome stability and may have implications for glioma treatment strategies. |
HostingRepository | PRIDE |
AnnounceDate | 2021-09-09 |
AnnouncementXML | Submission_2021-09-09_13:14:02.948.xml |
DigitalObjectIdentifier | https://dx.doi.org/10.6019/PXD022351 |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Supported dataset by repository |
PrimarySubmitter | Stephanie Byrum |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | monohydroxylated residue; iodoacetamide derivatized residue |
Instrument | Orbitrap Fusion Lumos |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-11-04 07:29:25 | ID requested | |
⏵ 1 | 2021-09-09 13:14:03 | announced | |
Publication List
Reed MR, Maddukuri L, Ketkar A, Byrum SD, Zafar MK, Bostian ACL, Tackett AJ, Eoff RL, Inhibition of tryptophan 2,3-dioxygenase impairs DNA damage tolerance and repair in glioma cells. NAR Cancer, 3(2):zcab014(2021) [pubmed] |
Keyword List
submitter keyword: DNA damage, DNA replication, DNA repair, kynurenine, replication stress, tryptophan 2,3-dioxygenase |
Contact List
Robert L. Eoff |
contact affiliation | Department of Biochemistry and Molecular Biology, University of Arkansas for Medical Sciences, Little Rock, AR 72205, U.S.A |
contact email | RLEoff@uams.edu |
lab head | |
Stephanie Byrum |
contact affiliation | UAMS |
contact email | sbyrum@uams.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD022351
- Label: PRIDE project
- Name: Inhibition of tryptophan 2,3-dioxygenase impairs DNA damage tolerance and repair in glioma cells