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Critical Reviews in Biochemistry and Molecular Biology

Manasi S Apte, Julia Promisel Cooper
While most cancer cells rely on telomerase expression/re-activation for linear chromosome maintenance and sustained proliferation, a significant population of cancers (10-15%) employs telomerase-independent strategies, collectively dubbed Alternative Lengthening of Telomeres (ALT). Most ALT cells relax the usual role of telomeres as inhibitors of local homologous recombination while maintaining the ability of telomeres to prohibit local non-homologous end joining reactions. Here we review current concepts surrounding how ALT telomeres achieve this new balance via alterations in chromatin landscape, DNA damage repair processes and handling of telomeric transcription...
November 28, 2016: Critical Reviews in Biochemistry and Molecular Biology
Phoom Chairatana, Elizabeth M Nolan
In the intestine, the mucosal immune system plays essential roles in maintaining homeostasis between the host and microorganisms, and protecting the host from pathogenic invaders. Epithelial cells produce and release a variety of biomolecules into the mucosa and lumen that contribute to immunity. In this review, we focus on a subset of these remarkable host-defense factors - enteric α-defensins, select lectins, mucins, and secretory immunoglobulin A - that have the capacity to bind microbes and thereby contribute to barrier function in the human gut...
November 13, 2016: Critical Reviews in Biochemistry and Molecular Biology
Bartholomew P Roland, Todd R Graham
Cellular membranes display a diversity of functions that are conferred by the unique composition and organization of their proteins and lipids. One important aspect of lipid organization is the asymmetric distribution of phospholipids (PLs) across the plasma membrane. The unequal distribution of key PLs between the cytofacial and exofacial leaflets of the bilayer creates physical surface tension that can be used to bend the membrane; and like Ca(2+), a chemical gradient that can be used to transduce biochemical signals...
October 4, 2016: Critical Reviews in Biochemistry and Molecular Biology
Suneel A Narayanavari, Shreevathsa S Chilkunda, Zoltán Ivics, Zsuzsanna Izsvák
Sleeping Beauty (SB) is the first synthetic DNA transposon that was shown to be active in a wide variety of species. Here, we review studies from the last two decades addressing both basic biology and applications of this transposon. We discuss how host-transposon interaction modulates transposition at different steps of the transposition reaction. We also discuss how the transposon was translated for gene delivery and gene discovery purposes. We critically review the system in clinical, pre-clinical and non-clinical settings as a non-viral gene delivery tool in comparison with viral technologies...
October 4, 2016: Critical Reviews in Biochemistry and Molecular Biology
Ravikiran S Yedidi, Amatullah K Fatehi, Cordula Enenkel
The ubiquitin-proteasome system (UPS) plays a critical role in cellular protein homeostasis and is required for the turnover of short-lived and unwanted proteins, which are targeted by poly-ubiquitination for degradation. Proteasome is the key protease of UPS and consists of multiple subunits, which are organized into a catalytic core particle (CP) and a regulatory particle (RP). In Saccharomyces cerevisiae, proteasome holo-enzymes are engaged in degrading poly-ubiquitinated substrates and are mostly localized in the nucleus during cell proliferation...
September 28, 2016: Critical Reviews in Biochemistry and Molecular Biology
Marni S Crow, Krystal K Lum, Xinlei Sheng, Bokai Song, Ileana M Cristea
In mammalian cells, early defenses against infection by pathogens are mounted through a complex network of signaling pathways shepherded by immune-modulatory pattern-recognition receptors. As obligate parasites, the survival of viruses is dependent on the evolutionary acquisition of mechanisms that tactfully dismantle and subvert the cellular intrinsic and innate immune responses. Here, we review the diverse mechanisms by which viruses that accommodate DNA genomes are able to circumvent activation of cellular immunity...
September 21, 2016: Critical Reviews in Biochemistry and Molecular Biology
Julia E Gerson, Amrit Mudher, Rakez Kayed
The culmination of many years of increasing research into the toxicity of tau aggregation in neurodegenerative disease has led to the consensus that soluble, oligomeric forms of tau are likely the most toxic entities in disease. While tauopathies overlap in the presence of tau pathology, each disease has a unique combination of symptoms and pathological features; however, most study into tau has grouped tau oligomers and studied them as a homogenous population. Established evidence from the prion field combined with the most recent tau and amyloidogenic protein research suggests that tau is a prion-like protein, capable of seeding the spread of pathology throughout the brain...
September 21, 2016: Critical Reviews in Biochemistry and Molecular Biology
Noélia Custódio, Maria Carmo-Fonseca
Transcription and splicing are fundamental steps in gene expression. These processes have been studied intensively over the past four decades, and very recent findings are challenging some of the formerly established ideas. In particular, splicing was shown to occur much faster than previously thought, with the first spliced products observed as soon as splice junctions emerge from RNA polymerase II (Pol II). Splicing was also found coupled to a specific phosphorylation pattern of Pol II carboxyl-terminal domain (CTD), suggesting a new layer of complexity in the CTD code...
September 13, 2016: Critical Reviews in Biochemistry and Molecular Biology
James A Shapiro
The read-write genome idea predicts that mobile DNA elements will act in evolution to generate adaptive changes in organismal DNA. This prediction was examined in the context of mammalian adaptations involving regulatory non-coding RNAs, viviparous reproduction, early embryonic and stem cell development, the nervous system, and innate immunity. The evidence shows that mobile elements have played specific and sometimes major roles in mammalian adaptive evolution by generating regulatory sites in the DNA and providing interaction motifs in non-coding RNA...
September 7, 2016: Critical Reviews in Biochemistry and Molecular Biology
Julia Jellusova, Robert C Rickert
B cell growth and proliferation is tightly regulated by signaling through the B cell receptor and by other membrane bound receptors responding to different cytokines. The PI3K signaling pathway has been shown to play a crucial role in B cell activation, differentiation and survival. Activated B cells undergo metabolic reprograming in response to changing energetic and biosynthetic demands. B cells also need to be able to coordinate metabolic activity and proliferation with nutrient availability. The PI3K signaling network has been implicated in regulating nutrient acquisition, utilization and biosynthesis, thus integrating receptor-mediated signaling with cell metabolism...
September 2016: Critical Reviews in Biochemistry and Molecular Biology
Bhargavi Jayaraman, Amber M Smith, Jason D Fernandes, Alan D Frankel
Viruses are obligate parasites that rely heavily on host cellular processes for replication. The small number of proteins typically encoded by a virus is faced with selection pressures that lead to the evolution of distinctive structural properties, allowing each protein to maintain its function under constraints such as small genome size, high mutation rate, and rapidly changing fitness conditions. One common strategy for this evolution is to utilize small building blocks to generate protein oligomers that assemble in multiple ways, thereby diversifying protein function and regulation...
August 14, 2016: Critical Reviews in Biochemistry and Molecular Biology
Guido Keijzers, Dekang Liu, Lene Juel Rasmussen
Exonuclease 1 (EXO1) is a multifunctional 5' → 3' exonuclease and a DNA structure-specific DNA endonuclease. EXO1 plays roles in DNA replication, DNA mismatch repair (MMR) and DNA double-stranded break repair (DSBR) in lower and higher eukaryotes and contributes to meiosis, immunoglobulin maturation, and micro-mediated end-joining in higher eukaryotes. In human cells, EXO1 is also thought to play a role in telomere maintenance. Mutations in the human EXO1 gene correlate with increased susceptibility to some cancers...
August 5, 2016: Critical Reviews in Biochemistry and Molecular Biology
Joost Willebrords, Sara Crespo Yanguas, Michaël Maes, Elke Decrock, Nan Wang, Luc Leybaert, Brenda R Kwak, Colin R Green, Bruno Cogliati, Mathieu Vinken
Inflammation may be caused by a variety of factors and is a hallmark of a plethora of acute and chronic diseases. The purpose of inflammation is to eliminate the initial cell injury trigger, to clear out dead cells from damaged tissue and to initiate tissue regeneration. Despite the wealth of knowledge regarding the involvement of cellular communication in inflammation, studies on the role of connexin-based channels in this process have only begun to emerge in the last few years. In this paper, a state-of-the-art overview of the effects of inflammation on connexin signaling is provided...
July 7, 2016: Critical Reviews in Biochemistry and Molecular Biology
Magali de Bruyn, Jennifer Vandooren, Estefania Ugarte-Berzal, Ingrid Arijs, Séverine Vermeire, Ghislain Opdenakker
Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are thought to be predominant proteases and protease inhibitors involved in the pathogenesis of inflammatory bowel diseases (IBD) through their ability to remodel the extracellular matrix (ECM) in response to inflammatory stimuli and by their immunomodulating effects. An imbalance between MMPs and TIMPs has been linked with acute and chronic inflammation and aberrant tissue remodeling, as seen in IBD. Moreover, recurrent phases of tissue destruction and subsequent tissue repair can cause serious complications in IBD patients such as fistulas and fibrosis...
June 30, 2016: Critical Reviews in Biochemistry and Molecular Biology
Nina Y Yao, Mike E O'Donnell
The machines that decode and regulate genetic information require the translation, transcription and replication pathways essential to all living cells. Thus, it might be expected that all cells share the same basic machinery for these pathways that were inherited from the primordial ancestor cell from which they evolved. A clear example of this is found in the translation machinery that converts RNA sequence to protein. The translation process requires numerous structural and catalytic RNAs and proteins, the central factors of which are homologous in all three domains of life, bacteria, archaea and eukarya...
May 2016: Critical Reviews in Biochemistry and Molecular Biology
Lorraine S Symington
The repair of DNA double-strand breaks (DSBs) by homologous recombination (HR) is initiated by nucleolytic degradation of the 5'-terminated strands in a process termed end resection. End resection generates 3'-single-stranded DNA tails, substrates for Rad51 to catalyze homologous pairing and DNA strand exchange, and for activation of the DNA damage checkpoint. The commonly accepted view is that end resection occurs by a two-step mechanism. In the first step, Sae2/CtIP activates the Mre11-Rad50-Xrs2/Nbs1 (MRX/N) complex to endonucleolytically cleave the 5'-terminated DNA strands close to break ends, and in the second step Exo1 and/or Dna2 nucleases extend the resected tracts to produce long 3'-ssDNA-tailed intermediates...
May 2016: Critical Reviews in Biochemistry and Molecular Biology
Andrew J Kennedy, J David Sweatt
Over the past decade, since epigenetic mechanisms were first implicated in memory formation and synaptic plasticity, dynamic DNA methylation reactions have been identified as integral to long-term memory formation, maintenance, and recall. This review incorporates various new findings that DNA methylation mechanisms are important regulators of non-Hebbian plasticity mechanisms, suggesting that these epigenetic mechanisms are a fundamental link between synaptic plasticity and metaplasticity. Because the field of neuroepigenetics is so young and the biochemical tools necessary to probe gene-specific questions are just now being developed and used, this review also speculates about the direction and potential of therapeutics that target epigenetic mechanisms in the central nervous system and the unique pharmacokinetic and pharmacodynamic properties that epigenetic therapies may possess...
May 2016: Critical Reviews in Biochemistry and Molecular Biology
Nathan Wlodarchak, Yongna Xing
Protein phosphatase 2A (PP2A) plays a critical multi-faceted role in the regulation of the cell cycle. It is known to dephosphorylate over 300 substrates involved in the cell cycle, regulating almost all major pathways and cell cycle checkpoints. PP2A is involved in such diverse processes by the formation of structurally distinct families of holoenzymes, which are regulated spatially and temporally by specific regulators. Here, we review the involvement of PP2A in the regulation of three cell signaling pathways: wnt, mTOR and MAP kinase, as well as the G1→S transition, DNA synthesis and mitotic initiation...
May 2016: Critical Reviews in Biochemistry and Molecular Biology
Sherket B Peterson, Gerald W Hart
Diabetes is a debilitating metabolic disease that is riddled with complications that can cause blindness, renal failure, nerve damage, and cardiovascular disease. Poor glycemic control is thought to be a key initiator in the progression of diabetic complications. Hyperglycemia has been shown to increase flux through the hexosamine biosynthetic pathway (HBP) to initiate many of the toxic effects of glucose. The major endpoint of the HBP is the formation of uridine diphosphate β-D-N-acetylglucosamine (UDP-GlcNAc), the donor for protein O-GlcNAcylation, and complex extracellular glycosylation...
May 2016: Critical Reviews in Biochemistry and Molecular Biology
Akiko Hata, Risa Kashima
MicroRNAs (miRNAs) are integral to the gene regulatory network. A single miRNA is capable of controlling the expression of hundreds of protein coding genes and modulate a wide spectrum of biological functions, such as proliferation, differentiation, stress responses, DNA repair, cell adhesion, motility, inflammation, cell survival, senescence and apoptosis, all of which are fundamental to tumorigenesis. Overexpression, genetic amplification, and gain-of-function mutation of oncogenic miRNAs ("onco-miRs") as well as genetic deletion and loss-of-function mutation of tumor suppressor miRNAs ("suppressor-miRs") are linked to human cancer...
May 2016: Critical Reviews in Biochemistry and Molecular Biology
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