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  1. DNA Barcoding of Simulium asakoae (Diptera: Simuliidae) From Northern Thailand
    Low VL, Srisuka W, Saeung A, Tan TK, Ya'cob Z, Yeong YS, et al.
    J Med Entomol, 2020 09 07;57(5):1675-1678.
    PMID: 32333022 DOI: 10.1093/jme/tjaa081
    Previous studies suggested the presence of species complex in the so-called Simulium asakoae Takaoka & Davies (Diptera: Simuliidae) in Thailand due to its high morphological variability and genetic divergence. To investigate whether the true S. asakoae is present in Thailand, we performed a detailed morphological identification of S. asakoae and compared its DNA barcodes with the morphospecies S. asakoae from Myanmar and the typical S. asakoae from Malaysia. Phylogenetic analysis revealed the Thai materials analyzed in this study were indeed genetically similar with those from Myanmar and Malaysia, though genetic distances 0-2.27% were observed. We tentatively regard this divergence as intraspecific variation, and the automatic barcode gap discovery analysis further supports them as a single species.
    Matched MeSH terms: DNA Barcoding, Taxonomic
  2. Fulltext Ageing, Drosophila melanogaster and Epigenetics
    Halim MA, Tan FHP, Azlan A, Rasyid II, Rosli N, Shamsuddin S, et al.
    Malays J Med Sci, 2020 May;27(3):7-19.
    PMID: 32684802 MyJurnal DOI: 10.21315/mjms2020.27.3.2
    Ageing is a phenomenon where the accumulation of all the stresses that alter the functions of living organisms, halter them from maintaining their physiological balance and eventually lead to death. The emergence of epigenetic tremendously contributed to the knowledge of ageing. Epigenetic changes in cells or tissues like deoxyribonucleic acid (DNA) methylation, modification of histone proteins, transcriptional modification and also the involvement of non-coding DNA has been documented to be associated with ageing. In order to study ageing, scientists have taken advantage of several potential organisms to aid them in their study. Drosophila melanogaster has been an essential model in establishing current understanding of the mechanism of ageing as they possess several advantages over other competitors like having homologues to more than 75% of human disease genes, having 50% of Drosophila genes are homologues to human genes and most importantly they are genetically amenable. Here, we would like to summarise the extant knowledge about ageing and epigenetic process and the role of Drosophila as an ideal model to study epigenetics in association with ageing process.
    Matched MeSH terms: DNA
  3. Fulltext Fasciolasis in Tuaran, Sabah: A Case Report
    Bizini, Fionna Vincent
    Borneo Journal of Medical Sciences, 2018;12(101):35-36.
    MyJurnal
    Fascioliasis is a major parasitic disease caused by the liver flukes, Fasciola hepatica and Fasciola gigantica in Malaysia. On 31st May 2016, three cases of fasciolasis among humans were notified in Tuaran involving two localities.
    Matched MeSH terms: DNA, Helminth
  4. Fulltext The chromosomal DNA damage in buccal mucosa cells among schools children in the vicinity of mobile base stations in Selangor
    Raihanah Chokeli, Nur Azira Baharuddin, Vivien How, Nurul Syazani Yuswir, Shariza Afini Mohd Noor, Ho Yu Bin, et al.
    Malaysian Journal of Medicine and Health Sciences, 2019;15(204):124-129.
    MyJurnal
    Introduction: The increased use of mobile phones has increased the mobile base stations (MBS) deployment. While understanding of radiation protection is growing among the public, questions regarding early-life exposure to ra- diofrequency radiation (RFR) from MBS in children are of importance as to whether it will raise the chances of developing chronic diseases during adulthood. Taking into account the sitting location of MBS, the purpose of this study is to evaluate the chromosomal DNA damage in buccal mucosal cells between school children exposed to RFR emitted from base station antennas. Method: This is a comparative cross-sectional study in which two group of school children were sampled i.e. exposed groups are children whose school located near MBS (200 meters); un- exposed groups are children whose school located distant far from the MBS (>200 meters). Digital RF Analyzer was used to measure RFR at the school surrounding. Buccal mucosa cells from the oral cavity were sampled to examine the level of micronuclei (MN) frequencies. Results: This study found that the densities of the RFR energy differed in range. Although all measurements showed the RFR reading below the acceptable exposure level, there were still sig- nificant variations at each location assessed. Statistically, the MN frequency is significantly different when compared to the exposed and non-exposed group. Conclusion: To understand the mechanism of health effects from exposure to low-level RFR emited from MBS, further study should consider environmental factors influencing MBS sitting on RFR emission, as well as examining the health effects into molecular levels.
    Matched MeSH terms: DNA Damage
  5. Fulltext A mini-review on the effects of COVID-19 on younger individuals
    Manivannan M, Jogalekar MP, Kavitha MS, Maran BAV, Gangadaran P
    Exp Biol Med (Maywood), 2021 02;246(3):293-297.
    PMID: 33210552 DOI: 10.1177/1535370220975118
    Coronavirus disease 2019 (COVID-19) pandemic has uprooted our lives like never before since its onset in the late December 2019. The world has seen mounting infections and deaths over the past few months despite the unprecedented measures countries are implementing, such as lockdowns, social distancing, mask-wearing, and banning gatherings in large groups. Interestingly, young individuals seem less likely to be impacted by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19. While the rate of transmission, symptom presentation, and fatality is lower in children than people from other age groups, they have been disproportionately affected by strict lockdown measures needed to curb viral spread. In this review, we describe the association between patient age and COVID-19, epidemiology of SARS-CoV-2 infection in children, psychological effects associated with lockdowns and school closures, and possible mechanisms underlying lower transmission rate of COVID-19 in children.
    Matched MeSH terms: DNA Viruses
  6. Fulltext Complete mitochondrial genome of six Cheilinus undulatus (Napoleon Wrasse): an endangered marine fish species from Sabah, Malaysia
    Matthew P, Manjaji-Matsumoto BM, Rodrigues KF
    Mitochondrial DNA B Resour, 2018 Oct 12;3(2):943-944.
    PMID: 33474374 DOI: 10.1080/23802359.2018.1473725
    We report here the complete mitochondrial (mt) genomes of six individuals of Cheilinus undulatus (Napoleon Wrasse), an endangered marine fish species. The six mt DNA sequences had an average size of 17,000 kb and encoded 22 tRNA, two sRNA, 13 highly conserved protein coding genes and a control region. The polymorphic variation (control region) in these six individuals suggests their potential use as a specific marker for phylogeographic conservation. Moreover, the sequence polymorphism within the control region (D-loop) suggests that this locus can be applied for phylogenetic studies.
    Matched MeSH terms: DNA, Mitochondrial
  7. Fulltext The complete mitochondrial genome of Varuna yui (Decapoda: Brachyura: Varunidae) and its phylogeny
    Lin F, Xie Z, Fazhan H, Baylon JC, Yang X, Tan H, et al.
    Mitochondrial DNA B Resour, 2018 Feb 23;3(1):263-264.
    PMID: 33474136 DOI: 10.1080/23802359.2018.1443043
    The complete mitochondrial genome plays an important role in the research on phylogenetic relationship. Here, we reported the first complete mitochondrial genome sequence of Varuna yui Hwang & Takeda, 1986 (Varunidae). The complete mtDNA (15,915 bp in length) consisted of 13 protein-coding genes, 22 tRNAs, two rRNA genes, and a control region. The gene arrangement was identical to those observed in the Varunidae species. The phylogenetic analysis suggested that V. yui had close relationship with other Varunidae species (Helicetient sinensis, Eriocher sinesis, etc.). The newly described genome may facilitate further comparative mitogenomic analysis within Varunidae species.
    Matched MeSH terms: DNA, Mitochondrial
  8. Genomic Instability and Cellular Senescence: Lessons From the Budding Yeast
    Lee JW, Ong EBB
    Front Cell Dev Biol, 2020;8:619126.
    PMID: 33511130 DOI: 10.3389/fcell.2020.619126
    Aging is a complex biological process that occurs in all living organisms. Aging is initiated by the gradual accumulation of biomolecular damage in cells leading to the loss of cellular function and ultimately death. Cellular senescence is one such pathway that leads to aging. The accumulation of nucleic acid damage and genetic alterations that activate permanent cell-cycle arrest triggers the process of senescence. Cellular senescence can result from telomere erosion and ribosomal DNA instability. In this review, we summarize the molecular mechanisms of telomere length homeostasis and ribosomal DNA stability, and describe how these mechanisms are linked to cellular senescence and longevity through lessons learned from budding yeast.
    Matched MeSH terms: DNA, Ribosomal
  9. Fulltext Pathogenic mutations in ARX, CDKL5and STXBP1genes are not associated with the early-onset epileptic encephalopathy in Malaysian pediatricpatients: A pilot study
    Ameerah Jaafar, Feizel Alsiddiq, Ling, King-Hwa
    Neuroscience Research Notes, 2018;1(3):5-17.
    MyJurnal
    Gene mutation is one of the etiologies of early-onset epileptic encephalopathy (EOEE), an age-dependent seizure in infants, which leads to brain defects. Previous studies have shown that several genes namely, aristalessrelated homeobox (ARX), cyclindependent kinaselike 5 (CDKL5) and syntaxinbinding protein 1 (STXBP1) are responsible for the pathophysiology of the syndrome. Thestudy involved 20 EOEE patients and 60 control subjects, which aimed toinvestigatethe clinical association of Malaysian EOEE subjects with 13 known pathogenic mutations in the genes of interest. In addition, the entire ARX exonic region was also sequenced for known and novel mutations. PCR specificity and efficiency were optimized using conventional PCR and High Resolution Melting Analysis (HRMA). All cases and approximately 10% of control amplicon samples were purified and subjected to DNA sequencing. All known mutations reported previously were not found in control subjects and Malaysian EOEE patients with 100% confirmation by sequencing results. Sequencing of ARX exonic regionsof patient samplesdid not find any mutation in all exons. The preliminary study indicates that selected known pathogenic mutations of ARX, CDKL5and STXBP1are not associated with EOEE in Malaysian paediatric patients.
    Matched MeSH terms: Sequence Analysis, DNA
  10. Genome structure of Sagiyama virus and its relatedness to other alphaviruses
    Shirako Y, Yamaguchi Y
    J Gen Virol, 2000 May;81(Pt 5):1353-60.
    PMID: 10769079
    Sagiyama virus (SAG) is a member of the genus Alphavirus in the family Togaviridae, isolated in Japan from mosquitoes in 1956. We determined the complete nucleotide sequence of the SAG genomic RNA from the original stock virus which formed a mixture of plaques with different sizes, and that from a full-length cDNA clone, pSAG2, infectious RNA transcripts from which formed uniform large plaques on BHK-21 cells. The SAG genome was 11698 nt in length exclusive of the 3' poly(A) tail. Between the complete nucleotide sequences of the full-length cDNA clone, pSAG2, and the consensus sequence from the original stock virus, there were nine amino acid differences; two each in nsP1, nsP2 and E1, and three in E2, some of which may be responsible for plaque phenotypic variants in the original virus stock. SAG was most closely related to Ross River virus among other alphaviruses fully sequenced, with amino acid sequence identities of 86% in the nonstructural proteins and of 83% in the structural proteins. The 3' terminal 280 nt region of SAG was 82% identical to that of Barmah Forest virus, which was otherwise not closely related to SAG. Comparison of the nucleotide sequence of SAG with partial nucleotide sequences of Getah virus (GET), which was originally isolated in Malaysia in 1955 and is closely related to SAG in serology and in biology, showed near identity between the two viruses, suggesting that SAG is a strain of GET.
    Matched MeSH terms: DNA-Directed RNA Polymerases*; Sequence Analysis, DNA; DNA, Complementary
  11. Nucleotide sequence of precore region of hepatitis B virus DNA in HBsAg-positive carriers in Malaysia
    Ton SH, Iskandar K, Noriah R, Thanaletchimy N
    Scand. J. Infect. Dis., 1996;28(6):543-8.
    PMID: 9060053
    As most published studies on precore mutants have been carried out on isolates from patients with liver diseases, and it is unclear whether HBsAg carriers with viraemia in the absence of HBeAg are also generally infected by such mutants, it was decided to sequence the precore region in some HBV-DNA isolated from HBsAg-positive carriers. Precore sequences of HBV-DNA from 43 HBsAg carriers in Malaysia were studied. Three HBV subtypes were identified according to the nucleotide sequence of the precore region. Most of the carriers were found to be infected by the subtype adr. Mutations were detected in the precore regions. The most common conserved mutation was a silent mutation involving conversion from T to C (CCT to CCC) at position 1858 at codon 15 (proline). It was found that 4/43 (9.3%) had a mutation at the penultimate codon where TGG was changed to TAG. All 4 isolates with the TAG mutation had nt T at position 1858. Of the 4 carriers who were infected by these mutant viruses, 2 were coinfected with the wild type, 1 was infected only by a variant with the mutation at position 1896, while another was infected by a variant with mutations at positions 1896 and 1899. Three of the 4 were anti-HBe positive while 1 was HBeAg positive. Alanine aminotransaminase activities in all 4 carriers were normal. This study therefore demonstrated that variants with stop codons at the penultimate codon could be found in asymptomatic carriers in Malaysia.
    Matched MeSH terms: DNA Mutational Analysis; DNA, Viral/genetics*; DNA, Viral/isolation & purification
  12. Improvement in the detection rate of t(14;18) translocation on paraffin-embedded tissue: a combination approach using PCR and FISH
    Shaminie J, Peh SC, Tan MJ
    Pathology, 2003 Oct;35(5):414-21.
    PMID: 14555386
    AIMS: PCR has been the primary method used for the detection of t(14;18) translocation in formalin-fixed, paraffin-embedded tissues. This technique mainly targets the well-characterised breakpoint regions in chromosomes 14 and 18. FISH is now applicable on paraffin tissue sections and has been suggested to be capable of detecting essentially 100% of t(14;18) translocated cases. In this study, we described the application of both PCR and FISH for the detection of t(14;18) translocation.

    METHODS: Fifty follicular lymphoma cases were retrieved from the files of the Department of Pathology, University of Malaya Medical Centre (UMMC). Nested PCR amplification of MBR/JH and mcr/JH was performed in these cases, and those cases that did not demonstrate the translocation were subjected to FISH analysis.

    RESULTS: Thirty cases (60%) had t(14;18) translocation detected by PCR, 25 (50%) had breakpoint with MBR and five (10%) involved mcr. Twenty cases without detectable t(14;18) translocation by PCR were analysed by FISH. Eleven cases were successfully probed, and four of them showed positive translocation signal.

    CONCLUSIONS: The combination of PCR and FISH analysis on paraffin tissue sections for the detection of t(14;18) translocation increases the sensitivity of detection from 60 to 68%. Problems encountered in our FISH analysis on tissue sections impose certain limitations in using this technique for retrospective screening of large number of samples. Therefore, we suggested the application of PCR as the first screening tool on retrospective archival materials, followed by FISH on those PCR-negative cases.

    Matched MeSH terms: DNA, Neoplasm/analysis; DNA Primers/chemistry
  13. Molecular characterization of Salmonella weltevreden isolated from poultry: evidence of conjugal transfer of plasmid and antibiotic resistance
    Radu S, Mutalib SA, Rusul G, Hassan Z, Yeang LK
    Microbios, 2001;104(407):39-47.
    PMID: 11229656
    Ten strains of Salmonella weltevreden isolated from poultry sources were examined and found to contain plasmid DNA ranging in size from 1.8 to 68.5 MD. All isolates were susceptible to carbenicillin, cephalothin, ceftriazone, gentamicin, kanamycin and nalidixic acid, but resistance to bacitracin (100%), penicillin G (100%), rifampicin (100%), sulphamethoxazole (100%), cefuroxime (80%) and tetracycline (60%) was recorded. The 55 MD plasmid of strain SW5 determined resistance to penicillin G and tetracycline, which was transmissible to the E. coli K12 recipient at a frequency of 3.52 x 10(-5) transconjugants per input donor cell. The results of arbitrarily primed polymerase chain reaction (AP-PCR), using two 10-mer oligonucleotides and PCR-ribotyping to differentiate between the ten strains of S. weltevreden were compared. The strains were separated into ten different genome types by AP-PCR but were indistinguishable by PCR-ribotyping. These results suggest that poultry may constitute a reservoir for disseminating antibiotic resistance and that AP-PCR may be a valuable tool for epidemiological studies.
    Matched MeSH terms: DNA, Bacterial/chemistry; DNA Primers/chemistry
  14. Isolation and characterization of cDNA clones encoding ADP-glucose pyrophosphorylase from sago palm (Metroxylon sagu)
    Au SL, Tan SH, Harikrishna K, Napis S
    J. Biochem. Mol. Biol. Biophys., 2002 Oct;6(5):301-8.
    PMID: 12385964
    Four ADP-glucose pyrophosphorylase cDNA clones were isolated from mature leaves and pith of sago palm by the polymerase chain reaction (PCR) technique. Three of them (agpp10, agpp12 and agpl19) encoded the AGP large subunit, while the fourth clone (agpl1) encoded the small subunit. agpp10 and agpp12 were isolated from pith, agpl19 was isolated from mature leaves, while agpl1 from both tissues. In addition, a full-length cDNA of agpl1 was successfully isolated from a cDNA library of mature leaves by a PCR-based screening technique. Semi-quantitative analysis suggests that agpp10 and agpp12 were detectable only in pith, agpl19 only in leaves, while agpl1 was expressed in both leaves and pith tissues.
    Matched MeSH terms: DNA Primers; DNA, Complementary/genetics*; DNA, Complementary/isolation & purification
  15. Cloning and expression of a novel lipase gene from Bacillus sphaericus 205y
    Rahman RN, Chin JH, Salleh AB, Basri M
    Mol Genet Genomics, 2003 May;269(2):252-60.
    PMID: 12756537
    A Bacillus sphaericus strain (205y) that produces an organic solvent-tolerant lipase was isolated in Port Dickson, Malaysia. The gene for the lipase was recovered from a genomic library and sequenced. Phylogenetic analysis was performed based on an alignment of thirteen microbial lipase sequences obtained from the NCBI database. The analysis suggested that the B. sphaericus lipase gene is a novel gene, as it is distinct from other lipase genes in Families I.4 and I.5 reported so far. Expression in Escherichia coli under the control of the lacZ promoter resulted in an eight-fold increase in enzyme activity after a 3-h induction with 1 mM IPTG. The crude enzyme thus obtained showed a slight (10%) enhancement in activity after a 30-min incubation in 25% (v/v) n-hexane at 37 degrees C, and retained 90% of its activity after a similar period in 25% (v/v) p-xylene.
    Matched MeSH terms: DNA/metabolism; DNA Restriction Enzymes/metabolism
  16. Genetic variation of Trigonobalanus verticillata, a primitive species of Fagaceae, in Malaysia revealed by chloroplast sequences and AFLP markers
    Kamiya K, Harada K, Clyde MM, Mohamed AL
    Genes Genet Syst, 2002 Jun;77(3):177-86.
    PMID: 12207039
    The genetic variation of Trigonobalanus verticillata, the most recently described genus of Fagaceae, was studied using chloroplast DNA sequences and AFLP fingerprinting. This species has a restricted distribution that is known to include seven localities in tropical lower montane forests in Malaysia and Indonesia. A total of 75 individuals were collected from Bario, Kinabalu, and Fraser's Hill in Malaysia. The sequences of rbcL, matK, and three non-coding regions (atpB-rbcL spacer, trnL intron, and trnL-trnF spacer) were determined for 19 individuals from these populations. We found a total of 30 nucleotide substitutions and four length variations, which allowed identification of three haplotypes characterizing each population. No substitutions were detected within populations, while the tandem repeats in the trnL -trnF spacer had a variable repeat number of a 20-bp motif only in Kinabalu. The differentiation of the populations inferred from the cpDNA molecular clock calibrated with paleontological data was estimated to be 8.3 MYA between Bario and Kinabalu, and 16.7 MYA between Fraser's Hill and the other populations. In AFLP analysis, four selective primer pairs yielded a total of 431 loci, of which 340 (78.9%) were polymorphic. The results showed relatively high gene diversity (H(S) = 0.153 and H(T) = 0.198) and nucleotide diversity (pi(S) = 0.0132 and pi(T) = 0.0168) both within and among the populations. Although the cpDNA data suggest that little or no gene flow occurred between the populations via seeds, the fixation index estimated from AFLP data (F(ST) = 0.153 and N(ST) = 0.214) implies that some gene flow occurs between populations, possibly through pollen transfer.
    Matched MeSH terms: Sequence Analysis, DNA
  17. Six isoforms of cardiotoxin in malayan spitting cobra (Naja naja sputatrix) venom: cloning and characterization of cDNAs
    Jeyaseelan K, Armugam A, Lachumanan R, Tan CH, Tan NH
    Biochim. Biophys. Acta, 1998 Apr 10;1380(2):209-22.
    PMID: 9565688
    Cardiotoxins are the most abundant toxin components of cobra venom. Although many cardiotoxins have been purified and characterized by amino acid sequencing and other pharmacological and biochemical studies, to date only five cardiotoxin cDNAs from Taiwan cobra (Naja naja atra), three cDNAs from Chinese cobra (Naja atra) and two more of uncertain origin (either Chinese or Taiwan cobra) have been reported. In this paper we show the existence of four isoforms of cardiotoxin by protein analysis and nine cDNA sequences encoding six isoforms of cardiotoxins (CTX 1-3, 4a, 4b and 5) from N. n. sputatrix by cDNA cloning. This forms the first report on the cloning and characterization of several cardiotoxin genes from a single species of a spitting cobra. The cDNAs encoding these isoforms, obtained by reverse transcription-polymerase chain reaction (RT-PCR), were subsequently expressed in Escherichia coli. The native and recombinant cardiotoxins were first characterized by Western blotting and N-terminal protein sequencing. These proteins were also found to have different levels of cytolytic activity on cultured baby hamster kidney cells. Four of the isoforms (CTX 1, 2, 4 and 5) are unique to N. n. sputatrix, with CTX 2 being the most abundant species constituting about 50% of the total cardiotoxins. The isoform CTX 3 (20% constitution) is highly homologous to the cardiotoxins of N. n. atra and N. n. naja, indicating that it may be universally present in all Naja naja subspecies. Our studies suggest that the most hydrophilic isoform (CTX 5) could have evolved first followed by the hydrophobic isoforms (CTX 1, 2, 3 and 4). We also speculate that Asiatic cobras could be the modern descendants of the African and Egyptian counterparts.
    Matched MeSH terms: DNA, Complementary/analysis; DNA, Complementary/genetics; DNA, Complementary/chemistry
  18. Antibiotic resistance, plasmid profile and RAPD-PCR analysis of enteropathogenic Escherichia coli (EPEC) clinical isolates
    Wan KF, Radu S, Cheah YK, Benjamin PG, Ling CM, Hon SF, et al.
    Southeast Asian J Trop Med Public Health, 2003 Sep;34(3):620-6.
    PMID: 15115139
    Enteropathogenic Escherichia coli (EPEC) is a leading cause of diarrhea among infants in developing countries. A total of 38 EPEC isolates, obtained from diarrhea patients of Hospital Miri, Sarawak, were investigated through plasmid profile, antibiotic resistance and randomly amplified polymorphic DNA (RAPD) analysis. From the 8 types of antibiotics used, all isolates were 100% resistant to furoxime, cephalothin and sulphamethoxazole and showed high multiple antibiotic resistant (MAR) indexes, ranging from 0.5 to 1.0. In plasmid profiling, 22 isolates (58%) showed the presence of one or more plasmids in the range 1.0 to 30.9 mDa. The dendrogram obtained from the results of the RAPD-PCR discriminated the isolates into 30 single isolates and 3 clusters at the level of 40% similarity. The EPEC isolates were highly diverse, as shown by their differing plasmid profiles, antibiotic resistance patterns and RAPD profiles.
    Matched MeSH terms: DNA Fingerprinting/methods*; Random Amplified Polymorphic DNA Technique*
  19. Approaches towards the development of a vaccine against tuberculosis: recombinant BCG and DNA vaccine
    Mohd Nor N, Musa M
    Tuberculosis (Edinb), 2004;84(1-2):102-9.
    PMID: 14670351 DOI: 10.1016/j.tube.2003.08.011
    The last few years have witnessed intense research on vaccine development against tuberculosis. This has been driven by the upsurge of tuberculosis cases globally, especially those caused by multi-drug-resistant Mycobacterium tuberculosis strains. Various vaccine strategies are currently being developed which can be broadly divided into the so-called living and non-living vaccines. Examples are attenuated members of the M. tuberculosis complex, recombinant mycobacteria, subunit proteins and DNA vaccines. Given current developments, we anticipate that recombinant BCG and DNA vaccines are the most promising. Multiple epitopes of M. tuberculosis may need to be cloned in a vaccine construct for the desired efficacy to be achieved. The technique of assembly polymerase chain reaction could facilitate such a cloning procedure.
    Matched MeSH terms: Vaccines, DNA
  20. Fulltext A ruthenium polypyridyl intercalator stalls DNA replication forks, radiosensitizes human cancer cells and is enhanced by Chk1 inhibition
    Gill MR, Harun SN, Halder S, Boghozian RA, Ramadan K, Ahmad H, et al.
    Sci Rep, 2016 08 25;6:31973.
    PMID: 27558808 DOI: 10.1038/srep31973
    Ruthenium(II) polypyridyl complexes can intercalate DNA with high affinity and prevent cell proliferation; however, the direct impact of ruthenium-based intercalation on cellular DNA replication remains unknown. Here we show the multi-intercalator [Ru(dppz)2(PIP)](2+) (dppz = dipyridophenazine, PIP = 2-(phenyl)imidazo[4,5-f][1,10]phenanthroline) immediately stalls replication fork progression in HeLa human cervical cancer cells. In response to this replication blockade, the DNA damage response (DDR) cell signalling network is activated, with checkpoint kinase 1 (Chk1) activation indicating prolonged replication-associated DNA damage, and cell proliferation is inhibited by G1-S cell-cycle arrest. Co-incubation with a Chk1 inhibitor achieves synergistic apoptosis in cancer cells, with a significant increase in phospho(Ser139) histone H2AX (γ-H2AX) levels and foci indicating increased conversion of stalled replication forks to double-strand breaks (DSBs). Normal human epithelial cells remain unaffected by this concurrent treatment. Furthermore, pre-treatment of HeLa cells with [Ru(dppz)2(PIP)](2+) before external beam ionising radiation results in a supra-additive decrease in cell survival accompanied by increased γ-H2AX expression, indicating the compound functions as a radiosensitizer. Together, these results indicate ruthenium-based intercalation can block replication fork progression and demonstrate how these DNA-binding agents may be combined with DDR inhibitors or ionising radiation to achieve more efficient cancer cell killing.
    Matched MeSH terms: DNA/metabolism; DNA Damage/drug effects; DNA Damage/radiation effects; DNA Repair/drug effects; DNA Replication/drug effects*
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