PXD030459

PXD030459 is an original dataset announced via ProteomeXchange.

Title	Measurement of deaminated cytosine adducts in DNA using a novel hybrid thymine DNA glycosylase
Description	The hydrolytic deamination of cytosine and 5-methylcytosine drives many of the transition mutations observed in human cancer. The deamination-induced mutagenic intermediates are either uracil or thymine adducts mispaired with guanine. While a substantial array of methods exists to measure other types of DNA adducts, the cytosine deamination adducts pose unusual analytical problems and adequate methods to measure them have not yet been developed. We describe here a novel hybrid thymine DNA glycosylase, hyTDG, which is comprised of a 29-amino acid sequence from human thymine DNA glycosylase linked to a thymine glycosylase found in an archaeal thermophilic bacterium. Using defined-sequence oligonucleotides, we show that hyTDG has robust mispair-selective activity against deaminated U:G and T:G mispairs. We have further developed a method for separating glycosylase-released free bases from oligonucleotides and DNA followed by GC-MS/MS identification and quantification. Using this approach, we have measured for the first time the levels of total Uracil (U), U:G and T:G in calf thymus DNA. The method presented here will allow the measurement of the formation, persistence, and repair of a biologically important class of deaminated cytosine adducts.
HostingRepository	PRIDE
AnnounceDate	2024-10-22
AnnouncementXML	Submission_2024-10-22_05:32:14.725.xml
DigitalObjectIdentifier	https://dx.doi.org/10.6019/PXD030459
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Supported dataset by repository
PrimarySubmitter	Kangling Zhang
SpeciesList	scientific name: Homo sapiens (Human); NCBI TaxID: 9606;
ModificationList	acetylated residue
Instrument	Q Exactive

Revision	Datetime	Status	ChangeLog Entry
0	2021-12-16 12:16:39	ID requested
1	2022-02-16 08:24:22	announced
⏵ 2	2024-10-22 05:32:15	announced	2024-10-22: Updated project metadata.

10.6019/PXD030459;

submitter keyword: glycosylase, deamination, DNA repair, mass spectrometry,DNA damage, cytosine, mutation

Lawrence Sowers
contact affiliation	Department of Pharmacology and Toxicology, University of Texas Medical Branch Galveston, TX 77555
contact email	kazhang@utmb.edu
lab head
Kangling Zhang
contact affiliation	University of Texas Medical Branch
contact email	kazhang@utmb.edu
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD030459
     1. Label: PRIDE project
     2. Name: Measurement of deaminated cytosine adducts in DNA using a novel hybrid thymine DNA glycosylase