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Defective DNA repair and chromatin organization in patients with quiescent systemic lupus erythematosus

Overview of attention for article published in Arthritis Research & Therapy, August 2016
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Title
Defective DNA repair and chromatin organization in patients with quiescent systemic lupus erythematosus
Published in
Arthritis Research & Therapy, August 2016
DOI 10.1186/s13075-016-1081-3
Pubmed ID
Authors

Vassilis L. Souliotis, Konstantinos Vougas, Vassilis G. Gorgoulis, Petros P. Sfikakis

Abstract

Excessive autoantibody production characterizing systemic lupus erythematosus (SLE) occurs irrespective of the disease's clinical status and is linked to increased lymphocyte apoptosis. Herein, we tested the hypothesis that defective DNA damage repair contributes to increased apoptosis in SLE. We evaluated nucleotide excision repair at the N-ras locus, DNA double-strand breaks repair and apoptosis rates in peripheral blood mononuclear cells from anti-dsDNA autoantibody-positive patients (six with quiescent disease and six with proliferative nephritis) and matched healthy controls following ex vivo treatment with melphalan. Chromatin organization and expression levels of DNA repair- and apoptosis-associated genes were also studied in quiescent SLE. Defective nucleotide excision repair and DNA double-strand breaks repair were found in SLE, with lupus nephritis patients showing higher DNA damage levels than those with quiescent disease. Melphalan-induced apoptosis rates were higher in SLE than control cells and correlated inversely with DNA repair efficiency. Chromatin at the N-ras locus was more condensed in SLE than controls, while treatment with the histone deacetylase inhibitor vorinostat resulted in hyperacetylation of histone H4, chromatin decondensation, amelioration of DNA repair efficiency and decreased apoptosis. Accordingly, genes involved in DNA damage repair and signaling pathways, such as DDB1, ERCC2, XPA, XPC, MRE11A, RAD50, PARP1, MLH1, MLH3, and ATM were significantly underexpressed in SLE versus controls, whereas PPP1R15A, BARD1 and BBC3 genes implicated in apoptosis were significantly overexpressed. Epigenetically regulated functional abnormalities of DNA repair machinery occur in SLE, regardless of clinical disease activity, and may promote lymphocyte apoptosis. Approaches to correct these abnormalities may be of therapeutic value in SLE.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 30 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 30 100%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 6 20%
Student > Bachelor 3 10%
Researcher 3 10%
Student > Master 3 10%
Student > Doctoral Student 2 7%
Other 5 17%
Unknown 8 27%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 6 20%
Agricultural and Biological Sciences 6 20%
Medicine and Dentistry 5 17%
Pharmacology, Toxicology and Pharmaceutical Science 1 3%
Environmental Science 1 3%
Other 2 7%
Unknown 9 30%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 07 August 2016.
All research outputs
#22,759,802
of 25,374,647 outputs
Outputs from Arthritis Research & Therapy
#3,132
of 3,381 outputs
Outputs of similar age
#339,940
of 381,909 outputs
Outputs of similar age from Arthritis Research & Therapy
#43
of 50 outputs
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