Dataset Information

Analysis of protein interaction partners of TDIF

ABSTRACT: Reactive oxygen species (ROS) generated as by-products of metabolism can induce stochastic damage to cellular components including DNA. A localised oxidative damage may arise during transcriptional activation at promoters of protein coding genes. ROS are generated during oxidative demethylation of histones and 5-methyl cytosine in promoter CpG clusters. ROS induced oxidation of DNA bases, mainly 7,8-dihydro-8-oxoguanine (8-oxoG) is normally resolved through a well characterised repair pathway where the oxidised base is first removed by components of base excision repair (BER) pathway, and the resulting breaks in the DNA backbone are subsequently repaired by the single-strand repair (SSBR) machinery that includes TDP1 and XRCC1. In this project we have identified the role of a putative mitotic assembly protein, TDIF in ROS induced single strand break repair. Using semi-quantitative LC-MS/MS and biochemical assays we show that the long isoform of TDIF specifically interacts with SSBR machinery after oxidative damage.

INSTRUMENT(S): LTQ Orbitrap Elite

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Embryonic Stem Cell, Kidney

DISEASE(S): Disease Free

SUBMITTER: Adelina E Acosta-Martin

LAB HEAD: Sherif F El-Khamisy

PROVIDER: PXD018002 | Pride | 2022-10-12

REPOSITORIES: Pride

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Publications

A mechanism for oxidative damage repair at gene regulatory elements.

Ray Swagat S Abugable Arwa A AA Parker Jacob J Liversidge Kirsty K Palminha Nelma M NM Liao Chunyan C Acosta-Martin Adelina E AE Souza Cleide D S CDS Jurga Mateusz M Sudbery Ian I El-Khamisy Sherif F SF

Nature 20220928 7929

Oxidative genome damage is an unavoidable consequence of cellular metabolism. It arises at gene regulatory elements by epigenetic demethylation during transcriptional activation<sup>1,2</sup>. Here we show that promoters are protected from oxidative damage via a process mediated by the nuclear mitotic apparatus protein NuMA (also known as NUMA1). NuMA exhibits genomic occupancy approximately 100 bp around transcription start sites. It binds the initiating form of RNA polymerase II, pause-release ...[more]

PMID: 36171374

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Project description:The free radical theory of ageing is based on the idea that reactive oxygen species (ROS) may lead to the accumulation of age-related protein oxidation. Since the majority of cellular ROS is generated at the respiratory electron transport chain, this study focuses on the mitochondrial proteome of the ageing model Podospora anserina as target for ROS-induced damage. To ensure the detection of even low abundant modified peptides, separation by long gradient nLC-ESI-MS/MS and an appropriate statistical workflow for iTRAQ quantification was developed. Artificial protein oxidation was minimized by establishing gel-free sample preparation in the presence of reducing and iron-chelating agents. This first large scale, oxidative modification-centric study for P. anserina allowed the comprehensive quantification of 22 different oxidative amino acid modifications, and notably the quantitative comparison of oxidised and non-oxidised protein species. In total 2341 proteins were quantified. For 746 both protein species (unmodified and oxidatively modified) were detected and the modification sites determined. The data revealed that methionine residues are preferably oxidised. Further prominent identified modifications in decreasing order of occurrence were carbonylation as well as formation of N-formylkynurenine and pyrrolidinone. Interestingly, for the majority of proteins a positive correlation of changes in protein amount and oxidative damage were noticed, and a general decrease in protein amounts at late age. However, it was discovered that few proteins changed in oxidative damage in accordance with former reports. Our data suggest that P. anserina is efficiently capable to counteract ROS-induced protein damage during ageing as long as protein de-novo synthesis is functioning, ultimately leading to an overall constant relationship between damaged und undamaged protein species. These findings contradict a massive increase in protein oxidation during ageing and rather suggest a protein damage homeostasis mechanism even at late age.

Dataset Information

Analysis of protein interaction partners of TDIF

Publications

A mechanism for oxidative damage repair at gene regulatory elements.

Similar Datasets

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