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Mariana G. Braz Mariane A. P. Silva Drielle B. S. Figueiredo Aline G. Aun Lais S. K. Marques Juliana R. Lara Leandro G. Braz 《Environmental and molecular mutagenesis》2020,61(8):843-847
This study evaluated both telomere length (TL) and micronucleus (MN) as indicators of genome instability in 40 anesthesiologists occupationally exposed to anesthetics and in 40 physicians without occupational exposure to anesthetics who were matched by age, sex, and lifestyle. Blood and buccal samples were collected from both groups at the same period. Anesthetic exposure assessment was performed. The studied groups were assessed regarding relative TL by quantitative polymerase chain reaction and MN by buccal MN assay. Mean trace concentrations of anesthetics were below two parts per million. No significant differences between groups were found for both biomarkers. However, MN frequency was slightly increased (1.9-fold; p = .094) in the exposed group compared to the control group and in the exposed males (2.4-fold; p = .090) compared to unexposed males. TL and age showed a significant negative correlation. Anesthetic occupational exposure below recommended levels is not associated with changes in TL and MN in anesthesiologists. 相似文献
844.
Treacher Collins综合征(Treacher Collins syndrome,TCS;OMIM number 154500),是一种以常染色体显性遗传为主的先天颅面畸形疾病,其发病机制复杂.细胞质核糖体生物发生因子1(treacle ribosome biogenesis factor 1,TCOF1)是... 相似文献
845.
Laura Sabatino Nicoletta Botto Andrea Borghini Stefano Turchi Maria Grazia Andreassi 《Environmental and molecular mutagenesis》2013,54(5):299-307
Mitochondrial DNA (mtDNA) and telomere shortening have been proposed as important contributors to vascular disease and atherogenesis. The role of mitochondrial and telomere alterations has been examined frequently, but usually separately. Recently, an integrated model in which DNA damage and metabolic pathways intersect in age‐associated cardiovascular disease has been proposed. In this study we developed a fast and reliable real‐time PCR‐based procedure to investigate relative quantification of the 4,977 bp mitochondrial DNA deletion (also indicated as “mtDNA4977 deletion”), employing TaqMan probes with a multiplex approach. As a validation of the assay, a nested PCR coamplification was performed. Telomere shortening was evaluated by a real‐time monochrome multiplex PCR technique employing a SybrGreen‐based analysis. The study of mtDNA4977 deletion and telomere shortening was carried out in atrial biopsies from 11 patients undergoing coronary artery (n = 5) and valve surgery (n = 6). The relative quantifications showed that the amount of mtDNA4977 deletion was greater in tissue of patients with coronary artery disease (CAD) (P = 0.01) and that telomere length (expressed as telomere length relative to a single copy reference gene) was significantly shorter in tissue of CAD patients, compared to patients without CAD (P = 0.03). Moreover, most conventional risk factors were significantly more frequent in CAD patients, smoking and dyslipidemia having the strongest association with the degree of mtDNA4977deletion and a significant correlation with telomere attrition (P = 0.02 and P = 0.006, respectively). In conclusion, the present study suggests that mtDNA4977 deletion and telomere shortening may represent additional and synergic major risk factors for the pathogenesis of CAD and its complications. Environ. Mol. Mutagen. 54:299–307, 2013. © 2013 Wiley Periodicals, Inc. 相似文献
846.
Xavier Tadeo Jiyong Wang Scott P. Kallgren Jinqiang Liu Bharat D. Reddy Feng Qiao Songtao Jia 《Genes & development》2013,27(22):2489-2499
The RNAi pathway is required for heterochromatin assembly at repetitive DNA elements in diverse organisms. In fission yeast, loss of RNAi causes pericentric heterochromatin defects, compromising gene silencing and chromosome segregation. Here we show that deletion of telomere shelterin components restores pericentric heterochromatin and its functions in RNAi mutants. We further isolated a separation-of-function mutant of Poz1 and revealed that defective telomere silencing, but not telomere length control, is critical for bypassing RNAi. Further analyses demonstrated that compromising shelterin-mediated heterochromatin assembly in RNAi mutants releases heterochromatin protein Swi6, which is redistributed to pericentric regions through RNAi-independent heterochromatin assembly pathways. Given the high mobility of Swi6 protein and that increased levels of Swi6 facilitates heterochromatin spreading as well as ectopic heterochromatin assembly, our results suggest that constitutive heterochromatin domains use multiple pathways to form high-affinity platforms to restrain Swi6, thus limiting its availability and avoiding promiscuous heterochromatin formation. 相似文献
847.
Hyun-Ik Jun Jinqiang Liu Heetae Jeong Jin-Kwang Kim Feng Qiao 《Genes & development》2013,27(17):1917-1931
Telomeres are nucleoprotein complexes comprising telomeric DNA repeats bound by the multiprotein shelterin complex. A dynamic binary switch between telomerase-extendible and telomerase-nonextendible telomeric states determines telomere length homeostasis. However, the molecular nature of the nonextendible state is largely unknown. Here, we show that, in fission yeast, Tpz1 (the ortholog of human TPP1)-mediated complete linkage within the shelterin complex, bridging telomeric dsDNA to ssDNA, controls the telomerase-nonextendible state. Disruption of this linkage leads to unregulated telomere elongation while still retaining the shelterin components on telomeres. Therefore, the linkage within the shelterin components, rather than the individual shelterin components per se, defines the telomerase-nonextendible state. Furthermore, epistasis analyses reveal that Tpz1 also participates in the activation of telomeres to the extendible state via its interaction with Ccq1. Our results suggest critical regulatory roles of Tpz1 in the telomere binary switch. 相似文献
848.
849.
人端粒保护蛋白(human protection of telomeres,hPOT1)是一种端粒单链DNA结合蛋白,它结合于端粒末端的单链重复序列,在端粒长度的调控以及染色体的稳定方面起重要的作用。其表达水平下降所引起的端粒功能异常以及染色体畸变,与人类细胞的老化和恶性肿瘤的发生发展有密切的关系。对hPOT1结构、功能及作用机制的研究,不但可以进一步阐明细胞衰老和恶性肿瘤发生的分子机制,而且也将为肿瘤的诊断、治疗开辟新的思路和方法。 相似文献
850.
Miroslava Hancarova Marcela Malikova Michaela Kotrova Jana Drabova Marie Trkova Zdenek Sedlacek 《American journal of medical genetics. Part A》2018,176(6):1438-1442
Microdeletions of 17q24.2‐q24.3 have been described in several patients with developmental and speech delay, growth retardation, and other features. The relatively large size and limited overlap of the deletions complicate the genotype‐phenotype correlation. We identified a girl with intellectual disability, growth retardation, dysmorphic features, and a de novo 2.8 Mb long deletion of 17q24.2‐q24.3. Her phenotype was strikingly similar to one previously described boy with Dubowitz syndrome (MIM 223370) and a de novo 3.9 Mb long deletion encompassing the deletion of our patient. In addition, both patients had the shortest telomeres among normal age‐matched controls. Our review of all 17q24.2‐q24.3 deletion patients revealed additional remarkable phenotypic features shared by the patients, some of which have consequences for their management. Proposed novel genotype‐phenotype correlations based on new literature information on the region include the role of PSMD12 and BPTF, the genes recently associated with syndromic neurodevelopmental disorders, and a possible role of the complex topologically associated domain structure of the region, which may explain some of the phenotypic discrepancies observed between patients with similar but not identical deletions. Nevertheless, although different diagnoses including the Dubowitz, Nijmegen breakage (MIM 251260), Silver‐Russell (MIM 180860), or Myhre (MIM 139210) syndromes were originally considered in the 17q24.2‐q24.3 deletion patients, they clearly belong to one diagnostic entity defined by their deletions and characterized especially by developmental delay, specific facial dysmorphism, abnormalities of extremities and other phenotypes, and possibly also short telomere length. 相似文献