PXD021719

PXD021719 is an original dataset announced via ProteomeXchange.

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

Revision	Datetime	Status	ChangeLog Entry
0	2020-09-28 06:26:09	ID requested
⏵ 1	2020-12-21 03:41:47	announced

He X, Wang P, Wang Y, -Alkylthymidine Lesions. Anal Chem, 93(2):1161-1169(2021) [pubmed]

submitter keyword: Proteomics, LC-MS/MS, DNA Damage, TFAM

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

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/2020/12/PXD021719

PRIDE project URI

• PRIDE
  1. PXD021719
     1. Label: PRIDE project
     2. Name: TFAM Binds to and Promotes Mutagenic Transcriptional Bypass of O4-Alkylthymidine Lesions