PXD021719 is an
original dataset announced via ProteomeXchange.
Dataset Summary
Title | TFAM Binds to and Promotes Mutagenic Transcriptional Bypass of O4-Alkylthymidine Lesions |
Description | O2- and O4-alkylated thymidine lesions are known to be poorly repaired and persist in mammalian tissues. To understand how mammalian cells sense the presence and regulate the repair of these lesions, we employed a stable isotope labeling by amino acids in cell culture (SILAC)-based quantitative proteomic method to discover novel O2- and O4-n-butylthymidine (O2- and O4-nBudT)-binding proteins. We were able to identify 21 and 74 candidate DNA damage recognition proteins for O2-nBudT- and O4-nBudT-bearing DNA probes, respectively. Among these proteins, DDB1 and DDB2 selectively bind to O2-nBudT-containing DNA, whereas three HMG-box-containing proteins (i.e. HMGB1, HMGB2 and TFAM) exhibit preferential binding to O4-nBudT-bearing DNA. We further confirmed, by employing electrophoretic mobility shift assay, that TFAM can bind selectively and directly with O4-alkyldT-harboring DNA, and the binding capacity depends mainly on the HMG box-A domain of TFAM. We also found that TFAM promotes transcriptional mutagenesis of O4-alkyldT lesions in vitro and in human cells. Together, we explored, for the first time, the interactomes of O-alkyldT lesions. Our study also expands the functions of TFAM by revealing its capability in binding to O4-alkyldT-bearing DNA, demonstrating the role of HMG-box A domain in this molecular recognition, and uncovering its modulation of transcriptional mutagenesis of these lesions in human cells. |
HostingRepository | PRIDE |
AnnounceDate | 2020-12-21 |
AnnouncementXML | Submission_2020-12-21_03:41:46.xml |
DigitalObjectIdentifier | |
ReviewLevel | Peer-reviewed dataset |
DatasetOrigin | Original dataset |
RepositorySupport | Unsupported dataset by repository |
PrimarySubmitter | Xiaomei He |
SpeciesList | scientific name: Homo sapiens (Human); NCBI TaxID: 9606; |
ModificationList | No PTMs are included in the dataset |
Instrument | Q Exactive |
Dataset History
Revision | Datetime | Status | ChangeLog Entry |
0 | 2020-09-28 06:26:09 | ID requested | |
⏵ 1 | 2020-12-21 03:41:47 | announced | |
Publication List
He X, Wang P, Wang Y, -Alkylthymidine Lesions. Anal Chem, 93(2):1161-1169(2021) [pubmed] |
Keyword List
submitter keyword: Proteomics, LC-MS/MS, DNA Damage, TFAM |
Contact List
YINSHENG WANG |
contact affiliation | Department of Chemistry, University of California Riverside |
contact email | yinsheng@ucr.edu |
lab head | |
Xiaomei He |
contact affiliation | University of California, Riverside |
contact email | xiaomeih@ucr.edu |
dataset submitter | |
Full Dataset Link List
Dataset FTP location
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PRIDE project URI |
Repository Record List
[ + ]
[ - ]
- PRIDE
- PXD021719
- Label: PRIDE project
- Name: TFAM Binds to and Promotes Mutagenic Transcriptional Bypass of O4-Alkylthymidine Lesions