• BMB Reports
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• v.52 no.3
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• pp.175-180
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• 2019

Telomeres are nucleoprotein complexes at the physical ends of linear eukaryotic chromosomes. They protect the chromosome ends from various external attacks to avoid the loss of genetic information. Telomeres are maintained by cellular activities associated with telomerase and telomere-binding proteins. In addition, epigenetic regulators have pivotal roles in controlling the chromatin state at telomeres and subtelomeric regions, contributing to the maintenance of chromosomal homeostasis in yeast, animals, and plants. Here, we review the recent findings on chromatin modifications possibly associated with the dynamic states of telomeres in Arabidopsis thaliana.

• BMB Reports
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• v.47 no.1
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• pp.8-14
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• 2014

Telomerase plays a pivotal role in the pathology of aging and cancer by maintaining genome integrity, controlling cell proliferation, and regulating tissue homeostasis. Telomerase is essentially composed of an RNA component, Telomerase RNA or TERC, which serves as a template for telomeric DNA synthesis, and a catalytic subunit, telomerase reverse transcriptase (TERT). The canonical function of TERT is the synthesis of telomeric DNA repeats, and the maintenance of telomere length. However, accumulating evidence indicates that TERT may also have some fundamental functions that are independent of its enzymatic activity. Among these telomere-independent activities of hTERT, the role of hTERT in gene transcription has been investigated in detail. Transcriptional regulation is a fundamental process in biological systems. Several studies have shown a direct involvement of hTERT in gene transcription. This mini-review will focus on the role of hTERT in gene transcription regulation, and discuss its possible mechanisms.

• Molecules and Cells
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• v.19 no.3
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• pp.303-309
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• 2005

The end of eukaryotic genomic DNA is capped by a specialized structure called as "telomere" which consists of the repetitive array of nucleotide sequence, TTAGGG, in humans and mice, and a variety of binding proteins. Telomerase is a ribonucleoprotein (RNP) complex responsible for the elongation of telomeres to maintain the genomic integrity, and is composed of telomerase reverse transcriptase (TERT), telomerase RNA component (TERC), and their associated factors regulating the catalytic activity of telomerase. Although it is now apparent that telomerase protects cells from apoptosis via the maintenance of genomic integrity by stabilizing telomeres, our understanding for the physiological role of telomerase is yet far from completion, and emerging evidence suggests that telomerase has additional extratelomeric roles in mediating cell survival and anti-apoptotic functions against various cytotoxic stresses. Here we summarize and discuss how telomerase and telomeres are involved in mediating cellular protection against apoptosis.

• Proceedings of the Korean Society of Toxicology Conference
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• 2001.10a
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• pp.9-9
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• 2001

Several micronutrients (vitamins and minerals) are required as co-factors in DNA synthesis, DNA repair, DNA methylation and apoptosis. Some notable examples include (a) folic acid and vitamin B12 required for maintenance methylation of DNA and the synthesis of dTTP from dUTP, thus prevent the misincorporation of uracil into DNA, a highly mutagenic and chromosome-breaking event, (b) niacin, is essential in the form of the coenzymes NAD and NADP which act as a substrate for polyADPribose polymerase (PARP), an enzyme thought to facilitate efficient DNA repair and telomere length regulation and (c) zinc, apart from its antioxidant role as a co-factor in Cu/Zn SOD, it is required in its stabilizing role of the DNA-binding domain of p53 (residues 102-292) and thus is essential for apoptotic response to DNA damage. (omitted)

• Clinical and Experimental Pediatrics
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• v.57 no.8
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• pp.337-344
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• 2014

Inherited bone marrow failure syndrome (IBMFS) encompasses a heterogeneous and complex group of genetic disorders characterized by physical malformations, insufficient blood cell production, and increased risk of malignancies. They often have substantial phenotype overlap, and therefore, genotyping is often a critical means of establishing a diagnosis. Current advances in the field of IBMFSs have identified multiple genes associated with IBMFSs and their pathways: genes involved in ribosome biogenesis, such as those associated with Diamond-Blackfan anemia and Shwachman-Diamond syndrome; genes involved in telomere maintenance, such as dyskeratosis congenita genes; genes encoding neutrophil elastase or neutrophil adhesion and mobility associated with severe congenital neutropenia; and genes involved in DNA recombination repair, such as those associated with Fanconi anemia. Early and adequate genetic diagnosis is required for proper management and follow-up in clinical practice. Recent advances using new molecular technologies, including next generation sequencing (NGS), have helped identify new candidate genes associated with the development of bone marrow failure. Targeted NGS using panels of large numbers of genes is rapidly gaining potential for use as a cost-effective diagnostic tool for the identification of mutations in newly diagnosed patients. In this review, we have described recent insights into IBMFS and how they are advancing our understanding of the disease's pathophysiology; we have also discussed the possible implications they will have in clinical practice for Korean patients.

• Molecules and Cells
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• v.37 no.7
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• pp.526-531
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• 2014

Human PARP family consists of 17 members of which PARP-1 is a prominent member and plays a key role in DNA repair pathways. It has an N-terminal DNA-binding domain (DBD) encompassing the nuclear localisation signal (NLS), central automodification domain and C-terminal catalytic domain. PARP-1 accounts for majority of poly-(ADP-ribose) polymer synthesis that upon binding to numerous proteins including PARP itself modulates their activity. Reduced PARP-1 activity in ageing human samples and its deficiency leading to telomere shortening has been reported. Hence for cell survival, maintenance of genomic integrity and longevity presence of intact PARP-1 in the nucleus is paramount. Although localisation of full-length and truncated PARP-1 in PARP-1 proficient cells is well documented, subcellular distribution of PARP-1 fragments in the absence of endogenous PARP-1 is not known. Here we report the differential localisation of PARP-1 Nterminal fragment encompassing NLS in PARP-$1^{+/+}$ and PARP-$1^{-/-}$ mouse embryo fibroblasts by live imaging of cells transiently expressing EGFP tagged fragment. In PARP-$1^{+/+}$ cells the fragment localises to the nuclei presenting a granular pattern. Furthermore, it is densely packaged in the midsections of the nucleus. In contrast, the fragment localises exclusively to the cytoplasm in PARP-$1^{-/-}$ cells. Flourescence intensity analysis further confirmed this observation indicating that the N-terminal fragment requires endogenous PARP-1 for its nuclear transport. Our study illustrates the trafficking role of PARP-1 independently of its enzymatic activity and highlights the possibility that full-length PARP-1 may play a key role in the nuclear transport of its siblings and other molecules.