Human DNA repair diseases: From genome instability to cancer

Machado, Carlos Renato; Menck, C. F. M.

doi:10.1590/s0100-84551997000400032

Cited by 10 publications

(9 citation statements)

References 34 publications

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“…Other genes related to genetic stability In humans, various proteins involved in DNA repair are also related to hereditary diseases characterized by high chromosomal instability or a high incidence of cancer, or both (Machado and Menck, 1997). We looked for the presence of these proteins in the SUCEST database (Table VII) and found homologues for Ataxia Telangiectasia (Atm), Bloom (Blm) and Werner (Wrn) syndromes in agreement with previous findings in A. thaliana (The Arabidopsis Ge- 138 Costa et al …”

Section: Dna Replication and Damage Tolerance Pathwaysmentioning

confidence: 99%

DNA repair-related genes in sugarcane expressed sequence tags (ESTs)

et al. 2001

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There is much interest in the identification and characterization of genes involved in DNA repair because of their importance in the maintenance of the genome integrity. The high level of conservation of DNA repair genes means that these genetic elements may be used in phylogenetic studies as a source of information on the genetic origin and evolution of species. The mechanisms by which damaged DNA is repaired are well understood in bacteria, yeast and mammals, but much remains to be learned as regards plants. We identified genes involved in DNA repair mechanisms in sugarcane using a similarity search of the Brazilian Sugarcane Expressed Sequence Tag (SUCEST) database against known sequences deposited in other public databases (National Center of Biotechnology Information (NCBI) database and the Munich Information Center for Protein Sequences (MIPS) Arabidopsis thaliana database). This search revealed that most of the various proteins involved in DNA repair in sugarcane are similar to those found in other eukaryotes. However, we also identified certain intriguing features found only in plants, probably due to the independent evolution of this kingdom. The DNA repair mechanisms investigated include photoreactivation, base excision repair, nucleotide excision repair, mismatch repair, non-homologous end joining, homologous recombination repair and DNA lesion tolerance. We report the main differences found in the DNA repair machinery in plant cells as compared to other organisms. These differences point to potentially different strategies plants employ to deal with DNA damage, that deserve further investigation.

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Section: Dna Replication and Damage Tolerance Pathwaysmentioning

confidence: 99%

DNA repair-related genes in sugarcane expressed sequence tags (ESTs)

et al. 2001

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“…The Cockayne's syndrome (CS) and trichothiodystrophy (TTD) are further examples of NER deficiencies, whose clinical features are also sun sensitivity and mental retardation. 5 Patients with CS have a phenotype related to impaired transcriptional activity and, in contrast to XP, generally do not develop cancer, presumably because of the elimination of cells with DNA damage by apoptosis. 6 Mutations in the CSA and CSB genes were identified in most of the CS patients, and CS cells have been shown to be deficient in RNA synthesis recovery after UV and, more specifically, on the removal of CPDs by TCR.…”

Section: Introductionmentioning

confidence: 99%

Photorepair of RNA polymerase arrest and apoptosis after ultraviolet irradiation in normal and XPB deficient rodent cells

et al. 2002

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Cyclobutane pyrimidine dimers (CPDs) are directly involved in signaling for UV-induced apoptosis in mammalian cells. Failure to remove these lesions, specially those located at actively expressing genes, is critical, as cells defective in transcription coupled repair have increased apoptotic levels. Thus, the blockage of RNA synthesis by lesions is an important candidate event triggering off active cell death. In this work, wild-type and XPB mutated Chinese hamster ovary (CHO) cells expressing a marsupial photolyase, that removes specifically CPDs from the damaged DNA, were generated, in order to investigate the importance of this lesion in both RNA transcription blockage and apoptotic induction. Photorepair strongly recovers RNA synthesis in wild-type CHO cell line, although the resumption of transcription is decreased in XPB deficient cells. This recovery is accompanied by the prevention of cells entering into apoptosis. These results demonstrate that marsupial photolyase has access to CPDs blocking RNA synthesis in vivo, and this may be affected by the presence of a mutated XPB protein.

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“…The biological importance of the DNA repair mechanism in cancer development is illustrated by recessive autosomal disease such as chromosome fragility syndrome. Affected individuals, i.e., subjects with xeroderma pigmentosum, Fanconis anemia, or ataxia telangiectasia, are deficient in a type of repair and are at high risk for malignancy when exposed to specific mutagens such as UV light, alkylating agents and ionizing radiation (5). There are many cell repair mechanisms and, depending on the type of DNA lesion, a specific repair mechanism is initiated.…”

Section: Introductionmentioning

confidence: 99%

Evaluation of radioinduced damage and repair capacity in blood lymphocytes of breast cancer patients

Nascimento

Silva

Oliveira

et al. 2001

Braz J Med Biol Res

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Genetic damage caused by ionizing radiation and repair capacity of blood lymphocytes from 3 breast cancer patients and 3 healthy donors were investigated using the comet assay. The comets were analyzed by two parameters: comet tail length and visual classification. Blood samples from the donors were irradiated in vitro with a 60 Co source at a dose rate of 0.722 Gy/min, with a dose range of 0.2 to 4.0 Gy and analyzed immediately after the procedure and 3 and 24 h later. The basal level of damage and the radioinduced damage were higher in lymphocytes from breast cancer patients than in lymphocytes from healthy donors. The radioinduced damage showed that the two groups had a similar response when analyzed immediately after the irradiations. Therefore, while the healthy donors presented a considerable reduction of damage after 3 h, the patients had a higher residual damage even 24 h after exposure. The repair capacity of blood lymphocytes from the patients was slower than that of lymphocytes from healthy donors. The possible influence of age, disease stage and mutations in the BRCA1 and BRCA2 genes are discussed. Both parameters adopted proved to be sensitive and reproducible: the doseresponse curves for DNA migration can be used not only for the analysis of cellular response but also for monitoring therapeutic interventions. Lymphocytes from the breast cancer patients presented an initial radiosensitivity similar to that of healthy subjects but a deficient repair mechanism made them more vulnerable to the genotoxic action of ionizing radiation. However, since lymphocytes from only 3 patients and 3 normal subjects were analyzed in the present paper, additional donors will be necessary for a more accurate evaluation.

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Human DNA repair diseases: From genome instability to cancer

Cited by 10 publications

References 34 publications

DNA repair-related genes in sugarcane expressed sequence tags (ESTs)

DNA repair-related genes in sugarcane expressed sequence tags (ESTs)

Photorepair of RNA polymerase arrest and apoptosis after ultraviolet irradiation in normal and XPB deficient rodent cells

Evaluation of radioinduced damage and repair capacity in blood lymphocytes of breast cancer patients

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