BioEssays

Fairbrother, Will; Lipscombe, Diane

doi: 10.1002/bies.20696pmid: 18081004

A myriad of coordinated signals control cellular differentiation. Reprogramming the cell's proteome drives global changes in cell morphology and function that define cell phenotype. A switch in alternative splicing of many pre‐mRNAs encoding neuronal‐specific proteins accompanies neuronal differentiation. Three groups recently showed that the global splicing repressor, polypyrimidine track‐binding protein (PTB), regulates this switch.1–3 Although a subset of neuronal genes are turned on in both non‐neuronal and neuronal cells, restricted expression of PTB in non‐neuronal cells diverts their mRNAs to nonsense‐mediated decay and prevents protein expression. When the PTB brake is released, the cell splices like a neuron. BioEssays 30:1–4, 2008. © 2007 Wiley Periodicals, Inc.

Ball, Alexander R.; Yokomori, Kyoko

doi: 10.1002/bies.20691pmid: 18081005

Cohesin establishes sister‐chromatid cohesion during S phase to ensure proper chromosome segregation in mitosis. It also facilitates postreplicative homologous recombination repair of DNA double‐strand breaks by promoting local pairing of damaged and intact sister chromatids. In G2 phase, cohesin that is not bound to chromatin is inactivated, but its reactivation can occur in response to DNA damage. Recent papers by Koshland's and Sjögren's groups describe the critical role of the known cohesin cofactor Eco1 (Ctf7) and ATR checkpoint kinase in damage‐induced reactivation of cohesin, revealing an intricate mechanism that regulates sister‐chromatid pairing to maintain genome integrity.1,2 BioEssays 30:5–9, 2008. © 2007 Wiley Periodicals, Inc.

Koushika, Sandhya P.

doi: 10.1002/bies.20695pmid: 18081006

JIPs are JNK interacting proteins and bind to JNK cascade kinases. JIP1 and JIP3 were known to be adaptors linking cargo to Kinesin‐I, a major molecular motor for axonal transport. Recent research sheds further light on JIPs' complex roles in axonal transport, namely in activation of Kinesin‐I and in cargo release. In Drosophila, APLIP1/JIP1 allows the Kinesin‐I complex to enable cargo release through activation of JNK signaling.1 In mammalian cell culture, JIP1 is necessary and, together with UNC‐76/FEZ1, sufficient for activating Kinesin‐I.2 I discuss and compare the many roles played by JIP1 and JIP3 through interactions with several distinct players, in retrograde as well as anterograde transport. BioEssays 30:10–14, 2008. © 2007 Wiley Periodicals, Inc.

Smith, Catharine L.

doi: 10.1002/bies.20687pmid: 18081007

Transcriptional repression and silencing have been strongly associated with hypoacetylation of histones. Accordingly, histone deacetylases, which remove acetyl groups from histones, have been shown to participate in mechanisms of transcriptional repression. Therefore, current models of the role of acetylation in transcriptional regulation focus on the acetylation status of histones and designate histone acetyltransferases, which add acetyl groups to histones, as transcriptional coactivators and histone deacetylases as corepressors. In recent years, an accumulation of studies have shown that these enzymes also target non‐histone proteins and that histone deacetylases have clear roles as coactivators at a variety of genes, some of which are key regulators of cell growth and survival. This review summarizes the evidence for histone deacetylases as coactivators and provides models of coactivation mechanisms, some of which integrate roles of acetylated histones and non‐histone proteins in transcription. BioEssays 30:15–24, 2008. © 2007 Wiley Periodicals, Inc.

Mason, James M.; Frydrychova, Radmila Capkova; Biessmann, Harald

doi: 10.1002/bies.20688pmid: 18081009

Drosophila telomeres comprise DNA sequences that differ dramatically from those of other eukaryotes. Telomere functions, however, are similar to those found in telomerase‐based telomeres, even though the underlying mechanisms may differ. Drosophila telomeres use arrays of retrotransposons to maintain chromosome length, while nearly all other eukaryotes rely on telomerase‐generated short repeats. Regardless of the DNA sequence, several end‐binding proteins are evolutionarily conserved. Away from the end, the Drosophila telomeric and subtelomeric DNA sequences are complexed with unique combinations of proteins that also modulate chromatin structure elsewhere in the genome. Maintaining and regulating the transcriptional activity of the telomeric retrotransposons in Drosophila requires specific chromatin structures and, while telomeric silencing spreads from the terminal repeats in yeast, the source of telomeric silencing in Drosophila is the subterminal arrays. However, the subterminal arrays in both species may be involved in telomere–telomere associations and/or communication. BioEssays 30:25–37, 2008. © 2007 Wiley Periodicals, Inc.

Kim, Eddo; Goren, Amir; Ast, Gil

doi: 10.1002/bies.20692pmid: 18081010

Alternative splicing is a well‐characterized mechanism by which multiple transcripts are generated from a single mRNA precursor. By allowing production of several protein isoforms from one pre‐mRNA, alternative splicing contributes to proteomic diversity. But what do we know about the origin of this mechanism? Do the same evolutionary forces apply to alternatively and constitutively splice exons? Do similar forces act on all types of alternative splicing? Are the products generated by alternative splicing functional? Why is “improper” recognition of exons and introns allowed by the splicing machinery? In this review, we summarize the current knowledge regarding these issues from an evolutionary perspective. BioEssays 30:38–47, 2008. © 2007 Wiley Periodicals, Inc.

Wang, Ting‐Fang; Chen, Li‐Tzu; Wang, Andrew H.‐J.

doi: 10.1002/bies.20694pmid: 18081011

The RecA family proteins mediate homologous recombination, a ubiquitous mechanism for repairing DNA double‐strand breaks (DSBs) and stalled replication forks. Members of this family include bacterial RecA, archaeal RadA and Rad51, and eukaryotic Rad51 and Dmc1. These proteins bind to single‐stranded DNA at a DSB site to form a presynaptic nucleoprotein filament, align this presynaptic filament with homologous sequences in another double‐stranded DNA segment, promote DNA strand exchange and then dissociate. It was generally accepted that RecA family proteins function throughout their catalytic cycles as right‐handed helical filaments with six protomers per helical turn. However, we recently reported that archaeal RadA proteins can also form an extended right‐handed filament with three monomers per helical turn and a left‐handed protein filament with four monomers per helical turn. Subsequent structural and functional analyses suggest that RecA family protein filaments, similar to the F1‐ATPase rotary motor, perform ATP‐dependent clockwise axial rotation during their catalytic cycles. This new hypothesis has opened a new avenue for understanding the molecular mechanism of RecA family proteins in homologous recombination. BioEssays 30:48–56, 2008. © 2007 Wiley Periodicals, Inc.

A. O'Malley, Maureen; Powell, Alexander; Davies, Jonathan F.; Calvert, Jane

doi: 10.1002/bies.20664pmid: 18081015

Synthetic biology is an increasingly high‐profile area of research that can be understood as encompassing three broad approaches towards the synthesis of living systems: DNA‐based device construction, genome‐driven cell engineering and protocell creation. Each approach is characterized by different aims, methods and constructs, in addition to a range of positions on intellectual property and regulatory regimes. We identify subtle but important differences between the schools in relation to their treatments of genetic determinism, cellular context and complexity. These distinctions tie into two broader issues that define synthetic biology: the relationships between biology and engineering, and between synthesis and analysis. These themes also illuminate synthetic biology's connections to genetic and other forms of biological engineering, as well as to systems biology. We suggest that all these knowledge‐making distinctions in synthetic biology raise fundamental questions about the nature of biological investigation and its relationship to the construction of biological components and systems. BioEssays 30:57–65, 2008. © 2007 Wiley Periodicals, Inc.

Loi, Pasqualino; Beaujean, Nathalie; Khochbin, Saadi; Fulka, Josef; Ptak, Grazyna

doi: 10.1002/bies.20684pmid: 18081016

Despite the progress achieved over the last decade after the birth of the first cloned mammal, the efficiency of reproductive cloning remains invariably low. However, research aiming at the use of nuclear transfer for the production of patient‐tailored stem cells for cell/tissue therapy is progressing rapidly. Yet, reproductive cloning has many potential implications for animal breeding, transgenic research and the conservation of endangered species. In this article we suggest that the changes in the epi‐/genotype observed in cloned embryos arise from unbalanced nuclear reprogramming between parental chromosomes. It is probable that the oocyte reprogramming machinery, devised for resident chromosomes, cannot target the paternal alleles of somatic cells. We, therefore, suggest that a reasonable approach to balance this asymmetry in nuclear reprogramming might involve the transient expression in donor cells of chromatin remodelling proteins, which are physiologically expressed during spermatogenesis, in order to induce a male‐specific chromatin organisation in the somatic cells before nuclear transfer. BioEssays 30:66–74, 2008. © 2007 Wiley Periodicals, Inc.

Savage, Natasha Saint; Schmidt, Wolfgang

doi: 10.1002/bies.20693pmid: 18081017

The fate of root epidermal cells is controlled by a complex interplay of transcriptional regulators, generating a genetically determined, position‐biased arrangement of root hair cells. This pattern is altered during postembryonic development and in response to environmental signals to confer developmental plasticity that acclimates the plant to the prevailing conditions. Based on the hypothesis that events downstream of this initial mechanism can modulate the pattern installed during embryogenesis, we have developed a reaction diffusion model that reproduces the root hair patterning previously observed experimentally. Under all growth conditions, an almost equal spacing between root hair forming cells was observed both in vitro and in silico, indicating that long‐range intercellular communication is crucial for the trichoblasts' decision to form a root hair. We assume that a hair growth promoter (HGP) is upregulated in root‐hair‐forming cells by a trichoblast‐specific component. Once established, HGP production is self‐enhancing. The autocatalytic regulation of HGP is antagonized by an HGP‐produced hair growth inhibitor (HGI). HGI is exported from trichoblasts and diffuses to neighboring cells, where it inhibits further HGP production and promotes the non‐hair cell fate. Under conditions of phosphate deficiency, we hypothesise that HGP production is increased and HGI diffusion rate is reduced, leading to a position‐independent formation of extra root hairs. BioEssays 30:75–81, 2008. © 2007 Wiley Periodicals, Inc.