Expression of double strand DNA breaks repair genes in pterygium

Introduction. Distribution of the following allelic variants of DNA repair genes: АТМ (rs664677), XRCC7 (rs7003908), and MLH1 (rs1799977) in the population of personnel of harmful and hazardous occupation has been studied. The studied polymorphisms are recognized as cancer-specific markers of various types and localization of malignant neoplasms, as well as markers of radiosensitivity/resistance to radiation exposure. Objectives of the work: to find out the significance of polymorphisms of repair genes of double-strand DNA breaks: XRCC7 (rs7003908), АТМ (rs664677), and mismatch repair: MLH1 (rs1799977) in the formation of an individual predisposition to the development of chronic diseases of the bronchopulmonary system in miners and personnel ofasbestos-cement plants. Materials and methods. Respondents of the study group was the personnel of asbestos-cement plants and miners with chronic bronchopulmonary disease; the control group was made up of personnel without diseases of the respiratory system. The genotypes of the following genes were determined by real-time polymerase chain reaction: АТМ (rs664677), XRCC7 (rs7003908), and MLH1 (rs1799977). Results. It was established that the minor alleles of ATM•T and MLH1•G, minor homozygote ATM•TT and heterozygote MLH1•AG are associated with the risk of developing chronic diseases of the bronchopulmonary system. It has been revealed that the dominant alleles of ATM•A, MLH1•A; dominant homozygotes ATM•AA; MLH1•AA and heterozygote ATM•AT contribute to resistance to the development of the respiratory system conditions. Conclusion. The following alleles: ATM•T (Р<=0,06, χ2=3,44; OR=1,44; 95 % Cl: 0,96–2,17); MLH1•G (Р<=0,002, χ2=5,06; OR=1,61; 95 % Cl: 1,04–2,49) and genotype: ATM•TT (Р<=0,01, χ2=6,61; OR=2,48; 95 % Cl: 1,16–5,31); MLH1•AG (Р<=0,002, χ2=9,00; OR=2,32; 95 % CI: 1,29–4,21) associated with the risk of bronchopulmonary conditions development have been established. Also alleles: ATM•A (Р<=0,06, χ2=3,44; OR=0,69; 95 % CI: 0,46–1,04); MLH1•A (Р<=0,002, χ2=5,06; OR=0,62; 95 % CI: 0,40–0,96) and genotype: MLH1•A/A (Р<=0,003, χ2=8,73; OR=0,43; 95 % CI: 0,24–0,79) that form resistance to the development of pulmonary system conditions in certain occupational groups have been established. Key words: SNP, ATM, XRCC7, MLH1, bronchopulmonary pathology.

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Fine-Structure Mapping of Meiosis-Specific Double-Strand DNA Breaks at a Recombination Hotspot Associated With an Insertion of Telomeric Sequences Upstream of the HIS4 Locus in Yeast

Genetics ◽

10.1093/genetics/143.3.1115 ◽

1996 ◽

Vol 143 (3) ◽

pp. 1115-1125 ◽

Cited By ~ 3

Author(s):

Fei Xu ◽

Thomas D Petes

Keyword(s):

Meiotic Recombination ◽

Hydroxyl Groups ◽

Sequence Specificity ◽

Structure Mapping ◽

Dna Breaks ◽

Exonuclease Iii ◽

Recombination Hotspot ◽

Telomeric Sequences ◽

Double Strand Dna Breaks ◽

Double Strand Dna

Abstract Meiotic recombination in Saccharomyces cerevisiae is initiated by double-strand DNA breaks (DSBs). Using two approaches, we mapped the position of DSBs associated with a recombination hotspot created by insertion of telomeric sequences into the region upstream of HIS4. We found that the breaks have no obvious sequence specificity and localize to a region of ~50 bp adjacent to the telomeric insertion. By mapping the breaks and by studies of the exonuclease III sensitivity of the broken ends, we conclude that most of the broken DNA molecules have blunt ends with 3′-hydroxyl groups.

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Inside Back Cover: Double-Strand DNA Breaks Induced by Paracyclophane Gold(I) Complexes (Chem. Eur. J. 26/2017)

Chemistry - A European Journal ◽

10.1002/chem.201700517 ◽

2017 ◽

Vol 23 (26) ◽

pp. 6459-6459

Author(s):

Sebastian Bestgen ◽

Carmen Seidl ◽

Thomas Wiesner ◽

Andreas Zimmer ◽

Martina Falk ◽

...

Keyword(s):

Dna Breaks ◽

Back Cover ◽

Double Strand Dna Breaks ◽

Double Strand Dna

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Nucleosomes Suppress the Formation of Double-strand DNA Breaks during Attempted Base Excision Repair of Clustered Oxidative Damages

Journal of Biological Chemistry ◽

10.1074/jbc.m114.571588 ◽

2014 ◽

Vol 289 (29) ◽

pp. 19881-19893 ◽

Cited By ~ 28

Author(s):

Wendy J. Cannan ◽

Betty P. Tsang ◽

Susan S. Wallace ◽

David S. Pederson

Keyword(s):

Base Excision Repair ◽

Excision Repair ◽

Dna Breaks ◽

Oxidative Damages ◽

Double Strand Dna Breaks ◽

Base Excision ◽

Double Strand Dna

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Roles of Caenorhabditis elegans WRN Helicase in DNA Damage Responses, and a Comparison with Its Mammalian Homolog: A Mini-Review

Gerontology ◽

10.1159/000439200 ◽

2015 ◽

Vol 62 (3) ◽

pp. 296-303 ◽

Cited By ~ 6

Author(s):

Jin-Sun Ryu ◽

Hyeon-Sook Koo

Keyword(s):

Dna Damage ◽

Caenorhabditis Elegans ◽

Werner Syndrome ◽

Model Organisms ◽

Current Status ◽

Helicase Domain ◽

Replication Forks ◽

Dna Breaks ◽

Double Strand Dna Breaks ◽

Double Strand Dna

Werner syndrome protein (WRN) is unusual among RecQ family DNA helicases in having an additional exonuclease activity. WRN is involved in the repair of double-strand DNA breaks via the homologous recombination and nonhomologous end joining pathways, and also in the base excision repair pathway. In addition, the protein promotes the recovery of stalled replication forks. The helicase activity is thought to unwind DNA duplexes, thereby moving replication forks or Holliday junctions. The targets of the exonuclease could be the nascent DNA strands at a replication fork or the ends of double-strand DNA breaks. However, it is not clear which enzyme activities are essential for repairing different types of DNA damage. Model organisms such as mice, flies, and worms deficient in WRN homologs have been investigated to understand the physiological results of defects in WRN activity. Premature aging, the most remarkable characteristic of Werner syndrome, is also seen in the mutant mice and worms, and hypersensitivity to DNA damage has been observed in WRN mutants of all three model organisms, pointing to conservation of the functions of WRN. In the nematode Caenorhabditis elegans, the WRN homolog contains a helicase domain but no exonuclease domain, so that this animal is very useful for studying the in vivo functions of the helicase without interference from the activity of the exonuclease. Here, we review the current status of investigations of C. elegans WRN-1 and discuss its functional differences from the mammalian homologs.

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