• Title/Summary/Keyword: DNA complex

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The activity - binding affinity relationship of topoisomerase I inhibitors by flexible docking with FlexiDock

  • Kim, Ji-Hyun;Park, In-Hee;Kim, Choon-Mi
    • Proceedings of the PSK Conference
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    • 2003.10b
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    • pp.159.1-159.1
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    • 2003
  • Human Topoisomerase I (topo I) helps the control of DNA supercoiling in cells by assisting breaking and religation of DNA strand. It is essential for cellular metabolism and survival, hence, a good target for a novel class of anticancer drugs. As topo I inhibitor binds to the DNA-topo I complex, the religation of DNA strand is suppressed which results in the death of the target cell. Seven compounds of H-Imidazo[4, 5-g]phthalazing-4, 9-dione derivatives with $IC_50$ in the range of 0.001 and 6.27 $\mu$M in 5 different cancer cells and four compounds of 7-chloro-6-quinazoline-5, 8-dione derivatives with positive and negative topo I inhibition activities were studied. (omitted)

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Expression of DNA-dependent Protein Kinase and Its Relationship with Epidermal Growth Factor Receptor Signaling in Metastatic Cancer Cell Lines (DNA-PK 및 표피성장인자수용체의 신호전달이 암전이에 미치는 영향)

  • Hwang Jee Young;Kim Sun Hee;Kang Chi Dug;Yoon Man Soo
    • Journal of Life Science
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    • v.15 no.3 s.70
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    • pp.406-414
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    • 2005
  • The genetic instability of cancer cells may be related to inappropriately activated DNA repair pathways. In present study, the modulated expression of DNA-dependent protein kinase (DNA-PK), a major DNA repair protein, in human cancer metastatic cells was tested. The expressions of Ku70/80, regulatory subunit of DNA-PK, and the Ku DNA-binding activity in various highly metastatic cell lines were higher than those in each parental cell line. Also, the expression of DNA-PKcs, catalytic subunit of DNA-PK, and the kinase activity of the whole DNA-PK complex in highly metastatic cells were significantly increased as compared to those of parental cells, suggesting that the enhanced DNA repair capacity of metastatic cells could be associated with aberrant use of DNA repair, which may mediate tumor progression and metastatic potential. Increased EGFR (epidermal growth factor receptor) signaling has been associated with tumor invasion and metastasis, and the linkage between EGFR-mediated signaling and DNA-PK has been suggested. This study showed that PKI166, the new EGFR tyrosine kinase inhibitor, modulated the expressions of Ku70/80 and DNA-PKcs and also revealed the chemosensitization effect of PKI166 against metastatic cells may be in part due to inhibition of Ku70/80. These results suggest that interference in EGFR signaling by EGFR inhibitor resulted in the impairment of DNA repair activity, and thus DNA-PK could be possible molecular targets for therapy against metastatic cancer cells.

Taxonomy of the Golovinomyces cynoglossi Complex (Erysiphales, Ascomycota) Disentangled by Phylogenetic Analyses and Reassessments of Morphological Traits

  • Braun, Uwe;Bradshaw, Michael;Zhao, Ting-Ting;Cho, Sung-Eun;Shin, Hyeon-Dong
    • Mycobiology
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    • v.46 no.3
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    • pp.192-204
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    • 2018
  • The name Golovinomyces cynoglossi s. lat. is traditionally applied to a complex of morphologically similar powdery mildews on hosts of the plant family Boraginaceae. The current species-level taxonomy within this complex is ambiguous due to the lack of phylogenetic examinations. The present study applied phylogenetic methods to clarify the taxonomy of G. cynoglossi s. lat. Phylogenetic analysis of rDNA ITS sequences retrieved from Asian, European and North American specimens revealed that G. cynoglossi s. lat. collections from different hosts involved several species in five clearly separated lineages. Clade I consists primarily of Golovinomyces cynoglossi s. str. on Cynoglossum. Clade III consists of Golovinomyces sequences retrieved from the host genera Symphytum and Pulmonaria. The taxa within clade III are now assigned to G. asperifoliorum comb. nov. Clade V encompasses G. cynoglossi s. lat. on the host genera Bothriospermum, Buglossoides, Echium, Myosotis, and Trigonotis. The taxa within clade V are now assigned to G. asperifolii comb. nov. The species concerned in this study were lecto- and epitypified to stabilize their nomenclature.

Identification and characterization of a rice MCM2 homologue required for DNA replycation

  • Cho, Jae-Han;Kim, Ho-Bang;Kim, Hyung-Sae;Choi, Sang-Bong
    • BMB Reports
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    • v.41 no.8
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    • pp.581-586
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    • 2008
  • The pre-replication complex (pre-RC), including the core hexameric MCM2-7 complex, ensures that the eukaryotic genome is replicated only once per cell division cycle. In this study, we identified a rice $\underline{m}ini\underline{c}hromosome$ $\underline{m}aintenance$ (MCM) homologue (OsMCM2) that functionally complemented fission yeast MCM2 (CDC19) mutants. We found OsMCM2 transcript expression in roots, leaves, and seeds, although expression levels differed slightly among the organs. Likewise, the OsMCM2 protein was ubiquitously expressed, but it was downregulated when nutritients were limiting, indicating that MCM2 expression (and therefore cell cycle progression) requires adequate nutrition. Yeast two-hybrid and GST pull-down assays demonstrated that OsMCM2 interacted with the COP9 signalosome 5 (CSN5). Taken as a whole, our results indicated that OsMCM2 functions as a subunit of the rice MCM complex and interacts with CSN5 during developmental regulation.

A Complex Cortical Malformation Caused by a Mutation in the Tubulin-Encoding TUBB3 Gene (튜불린 부호화 유전자인 TUBB3 돌연변이에서 나타난 복합 뇌피질 발달기형)

  • Yu Hyun Lee;Noh Hyuck Park
    • Journal of the Korean Society of Radiology
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    • v.81 no.5
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    • pp.1246-1249
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    • 2020
  • Tubulinopathy commonly refers to complex congenital and non-progressive brain malformations caused by mutations in the tubulin genes. Among tubulin-encoding genes, TUBB3 has rarely been reported as a cause of complex cortical malformations. Herein, we report a case of tubulinopathy in a 21-month-old boy who presented with delayed development. He could not walk on his own and was not able to speak more than five words. Physical examination revealed right esotropia and hypotonia of the lower extremities. MRI showed dysmorphic brainstem and dysmorphic and hypertrophic basal ganglia. The right thalamus was relatively smaller than the left one. The cerebellum showed disorganization of the cerebellar folia. DNA sequencing revealed a missense mutation of the TUBB3 gene.

Comparative Analysis of T4SS Molecular Architectures

  • Mishghan Zehra;Jiwon Heo;Jeong Min Chung;Clarissa L Durie
    • Journal of Microbiology and Biotechnology
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    • v.33 no.12
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    • pp.1543-1551
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    • 2023
  • The recently published high-resolution R388 T4SS structure provides exciting new details about the complete complex of T4SS, including the components making up the stalk and arches, numerous symmetry mismatches between regions of the complex, and an intriguing interpretation of the closed stalk and radial symmetry of the inner membrane complex, which is related to pilus biogenesis assembly. However, there are a few unidentified densities in the electron microscopy map and portions of the identified component sequences for which the structure is not yet known. It is also unclear how well this minimized DNA-transporting T4SS predicts the structure of other T4SSs, such as expanded systems and those that transport proteins rather than DNA. In this review, we evaluate what can be inferred from the recent high-resolution structure of the R388 T4SS with respect to the Cag and Dot/Icm systems. These systems were selected because, given what is currently known about these systems, we expect them to present most structural differences compared to the R388 T4SS structure. Furthermore, we discuss bacterial physiology and diversity, the T4SS structures and their variations between different bacterial species. These insights may prove beneficial for researchers who elucidate the structure and functions of T4SS in different bacterial species.