Related Experiment Video
Updated: May 3, 2026
Visualizing and Quantifying Endonuclease-Based Site-Specific DNA Damage
Published on: August 21, 2021
Patients with systemic sclerosis present increased DNA damage differentially associated with DNA repair gene
Gustavo Martelli Palomino1, Carmen L Bassi, Isabela J Wastowski
1From the Program of Basic and Applied Immunology, Faculdade de Medicina de Ribeirão Preto, University of São Paulo (FMRP-USP); Department of Basic Sciences in Health, Faculty of Medical Sciences, Federal University of Mato Grosso (UFMT); Department of Genetics, FMRP-USP; Department of Physics and Chemistry, Faculty of Pharmaceutical Sciences of Ribeirão Preto (FCFRP-USP); Department of Clinical and Toxicological Analyses, Faculty of Pharmaceutical Sciences, University Federal Rio Grande do Norte State (UFRN); Department of Medicine, FMRP-USP; Unit of Rheumatology, Department of Internal Medicine, Faculty of Medical Sciences, State University of Campinas, (UNICAMP), Brazil; Commissariat à l'Energie Atomique et aux Energies Alternatives, Institut des Maladies Emergentes et des Therapies Innovantes, Service de Recherches en Hemato-Immunologies, Hôpital Saint-Louis, Paris, France; Division of Rheumatology, Faculdade de Medicina, Universidade de São Paulo (FM-USP), São Paulo, Brazil.
Objective:
Patients with systemic sclerosis (SSc) exhibit increased toxicity when exposed to genotoxic agents. In our study, we evaluated DNA damage and polymorphic sites in 2 DNA repair genes (XRCC1 Arg399Gln and XRCC4 Ile401Thr) in patients with SSc.
Methods:
A total of 177 patients were studied for DNA repair gene polymorphisms. Fifty-six of them were also evaluated for DNA damage in peripheral blood cells using the comet assay.
Results:
Compared to controls, the patients as a whole or stratified into major clinical variants (limited or diffuse skin involvement), irrespective of the underlying treatment schedule, exhibited increased DNA damage. XRCC1 (rs: 25487) and XRCC4 (rs: 28360135) allele and genotype frequencies observed in patients with SSc were not significantly different from those observed in controls; however, the XRCC1 Arg399Gln allele was associated with increased DNA damage only in healthy controls and the XRCC4 Ile401Thr allele was associated with increased DNA damage in both patients and controls. Further, the XRCC1 Arg399Gln allele was associated with the presence of antinuclear antibody and anticentromere antibody. No association was observed between these DNA repair gene polymorphic sites and clinical features of patients with SSc.
Conclusion:
These results corroborate the presence of genomic instability in SSc peripheral blood cells, as evaluated by increased DNA damage, and show that polymorphic sites of the XRCC1 and XRCC4 DNA repair genes may differentially influence DNA damage and the development of autoantibodies.
More Related Videos
Related Concept Videos
01:38Nucleotide Excision Repair
Cells are regularly exposed to mutagens—factors in the environment that can damage DNA and generate mutations. UV radiation is one of the most common mutagens and is estimated to introduce a significant number of changes in DNA. These include bends or kinks in the structure, which can block DNA replication or transcription. If these errors are not fixed, the damage can cause mutations, which in turn can result in cancer or disease depending on which sequences are...
01:08Nucleotide Excision Repair
02:25Overview of DNA Repair
Chemically...
02:25Overview of DNA Repair
01:02Long-patch Base Excision Repair
01:20Mismatch Repair
The Mutator Protein Family Plays a Key Role in DNA Mismatch Repair
The human genome has more than 3 billion base pairs of DNA per cell. Prior to cell division, that vast amount of genetic...