Current Issues in Molecular Biology

868 KiB

Open AccessReview

The Nuclear Lamina as a Gene-silencing Hub

by Yuri Y. Shevelyov and Dmitry I. Nurminsky

Curr. Issues Mol. Biol. 2012, 14(1), 27-38; https://doi.org/10.21775/cimb.014.027 - 28 Jul 2011

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There is accumulating evidence that the nuclear periphery is a transcriptionally repressive compartment. A surprisingly large fraction of the genome is either in transient or permanent contact with nuclear envelope, where the majority of genes are maintained in a silent state, waiting to be awakened during cell differentiation. The integrity of the nuclear lamina and the histone deacetylase activity appear to be essential for gene repression at the nuclear periphery. However, the molecular mechanisms of silencing, as well as the events that lead to the activation of lamina-tethered genes, require further elucidation. This review summarizes recent advances in understanding of the mechanisms that link nuclear architecture, local chromatin structure, and gene regulation. Full article

879 KiB

Open AccessReview

Ribonucleotide Reductase as a Target to Control Apicomplexan Diseases

by James B. Munro and Joana C. Silva

Curr. Issues Mol. Biol. 2012, 14(1), 9-26; https://doi.org/10.21775/cimb.014.009 - 26 Jul 2011

Cited by 9 | Viewed by 763

Abstract

Malaria is caused by species in the apicomplexan genus Plasmodium, which infect hundreds of millions of people each year and kill close to one million. While malaria is the most notorious of the apicomplexan-caused diseases, other members of the eukaryotic phylum Apicomplexa are responsible for additional, albeit less well-known, diseases in humans, economically important livestock, and a variety of other vertebrates. Diseases such as babesiosis (hemolytic anemia), theileriosis and East Coast Fever, cryptosporidiosis, and toxoplasmosis are caused by the apicomplexans Babesia, Theileria, Cryptosporidium and Toxoplasma, respectively. In addition to the loss of human life, these diseases are responsible for losses of billions of dollars annually. Hence, the research into new drug targets remains a high priority. Ribonucleotide reductase (RNR) is an essential enzyme found in all domains of life. It is the only means by which de novo synthesis of deoxyribonucleotides occurs, without which DNA replication and repair cannot proceed. RNR has long been the target of antiviral, antibacterial and anti-cancer therapeutics. Herein, we review the chemotherapeutic methods used to inhibit RNR, with particular emphasis on the role of RNR inhibition in Apicomplexa, and in light of the novel RNR R2_e2 subunit recently identified in apicomplexan parasites. Full article

1260 KiB

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Efficient Cloning of Alternatively Polyadenylated Transcripts via Hybridization Capture PCR

by Theodoros N. Rampias, Emmanuel G.Fragoulis and Diamantis C. Sideris

Curr. Issues Mol. Biol. 2012, 14(1), 1-8; https://doi.org/10.21775/cimb.014.001 - 10 May 2011

Viewed by 433

Abstract

Cloning of alternatively polyadenylated transcripts is crucial for studying gene expression and function. Recent transcriptome analysis has mainly focused on large EST clone collections. However, EST sequencing techniques in many cases are incapable of isolating rare transcripts or address transcript variability. In most cases, 3' RACE is applied for the experimental identification of alternatively polyadenylated transcripts. However, its application may result in nonspecific amplification and false positive products due to the usage of a single gene specific primer. Additionally, internal poly(A) stretches primed by oligo(dT) primer in mRNAs with AU-rich 3'UTR may generate truncated cDNAs. To overcome these limitations, we have developed a simple and rapid approach combining SMART technology for the construction of a full length cDNA library and hybrid capture PCR for the selection and amplification of target cDNAs. Our strategy is characterized by enhanced specificity compared to other conventional RT-PCR and 3' RACE procedures. Full article

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Curr. Issues Mol. Biol., Volume 14, Issue 1 (January 2012) – 3 articles

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