Non-perturbative unification in the light of LEP results

We consider an alternative to conventional GUTs originally proposed by Maiani, Parisi and Petronzio, where owing to the existence of extra fermion generations at some intermediate scale, the gauge couplings become large at high energies. We first comment on how the non- supersymmetric version of this scenario is ruled out; we then consider the two-loop evolution of the couplings in the supersymmetric extension of this scenario, and check whether such a scenario is feasible in the light of the precies values of couplings now available from LEP.Comment: Latex file 7 pages+1 fig. (ps file appended after the latex file), CERN-TH.6913/9

Structure and stability of human telomeric sequence

Telomeric DNA of a variety of vertebrates including humans contains the tandem repeat d(TTAGGG)n. We have investigated the structural properties of the human telomeric repeat oligonucleotide models d(T2AG3)4, d(G3T2A)3G3, and d(G3T2AG3) using CD, gel electrophoresis, and chemical probing techniques. The sequences d(G3T2A)3G3 and d(T2AG3)4 assume an antiparallel G quartet structure by intramolecular folding, while the sequence d(G3T2AG3) also adopts an antiparallel G quartet structure but by dimerization of hairpins. In all the above cases, adenines are in the loop. The TTA loops are oriented at the same end of the G tetrad stem in the case of hairpin dimer. Further, the oligonucleotide d(G3T2AG3) forms a higher order structure by the association of two hairpin dimers via stacking of G tetrad planes. Here we show that N-7 of adenine in the hairpin dimer is Hoogsteen hydrogen-bonded. The partial reactivity of loop adenines with DEPC in d(T2AG3)4 suggests that the intramolecular G quartet structure is highly polymorphic and structures with different loop orientations and topologies are formed in solution. Intra- and interloop hydrogen bonding schemes for the TTA loops are proposed to account for the observed diethyl pyrocarbonate reactivities of adenines. Sodium-induced G quartet structures differ from their potassium-induced counterparts not only in stability but also in loop conformation and interactions. Thus, the overall structure and stability of telomeric sequences are modulated by the cation present, loop sequence, and the number of G tracts, which might be important for the telomere function

Poly purine.pyrimidine sequences upstream of the beta-galactosidase gene affect gene expression in Saccharomyces cerevisiae

BACKGROUND: Poly purine.pyrimidine sequences have the potential to adopt intramolecular triplex structures and are overrepresented upstream of genes in eukaryotes. These sequences may regulate gene expression by modulating the interaction of transcription factors with DNA sequences upstream of genes. RESULTS: A poly purine.pyrimidine sequence with the potential to adopt an intramolecular triplex DNA structure was designed. The sequence was inserted within a nucleosome positioned upstream of the β-galactosidase gene in yeast, Saccharomyces cerevisiae, between the cycl promoter and gal 10Upstream Activating Sequences (UASg). Upon derepression with galactose, β-galactosidase gene expression is reduced 12-fold in cells carrying single copy poly purine.pyrimidine sequences. This reduction in expression is correlated with reduced transcription. Furthermore, we show that plasmids carrying a poly purine.pyrimidine sequence are not specifically lost from yeast cells. CONCLUSION: We propose that a poly purine.pyrimidine sequence upstream of a gene affects transcription. Plasmids carrying this sequence are not specifically lost from cells and thus no additional effort is needed for the replication of these sequences in eukaryotic cells

Analysis of CAG/CTG triplet repeats in the human genome: implication in transcription factor gene regulation

Instability and polymorphism at several CAG/CTG trinucleotide repeat loci have been associated with human genetic disorders. In an attempt to identify novel sites that may be possible loci for expansion of CAG/CTG repeats, we searched all human sequences in the EMBL nucleotide sequence database for (CAG)5 and (CTG)5 repeats. We have identified 121 human DNA sequences of known and unknown functions that contain stretches of five or more CAG or CTG repeats. Many repeat stretches were interrupted by variant triplets, a significant number of which differ from the repeat triplet only by a single base, suggesting that these evolved from the parent triplet by point mutations. A large number of human transcription factor genes were found to contain CAG repeats within their coding sequences. Analysis of the EMBL transcription factors database showed that many transcription factor genes of other eukaryotes, including genes involved inDrosophila embryo development, possess these repeats. Interestingly, CAG repeats are absent from prokaryotic transcription factors. Different sequence entries for the human TATA box binding protein showed a polymorphism in the length of the CAG repeat in this gene, suggesting that loci other than those already known to be associated with genetic diseases may be possible sites for repeat instability related disorders. On the basis of our findings in this database analysis, we propose a role for CAG repeats as cisacting regulatory elements involved in fine-tuning gene expression

DNA chip the what's, the why's and the how's

This article presents a brief overview of DNA chips, or microarrays. Microarrays are a very significant technological development in molecular biology, and are perhaps the most efficient tool available for functional genomics today

Recent direct measurement of the Top quark mass and quasi-infrared fixed point

We note that the recent direct measurement of the top quark mass at $173.3 \pm 5.6 (stat) \pm 6.2 (syst)$ by D0 collaboration severely constrains the theoretically attractive infra-red fixed point scenario of the top quark Yukawa coupling in supersymmetric GUTs. For one-step unified models the above mentioned measurement bounds the arbitrary but experimentally determinable parameter $\tan \beta$ to the range $1.3 \le \tan \beta \le 2.1$. Further crunch on the top quark mass may determine $\tan \beta$ even more accurately within the fixed point scenario. On the other hand an experimental value of $\tan \beta > 2.1$ will rule out the fixed point scenario bounding $h^2_t(M_X)/4 \pi$ to 0.022 from above.Comment: 7 pages, Latex with epsf style, 1 figure, captions.st

(TG/CA)(n )repeats in human gene families: abundance and selective patterns of distribution according to function and gene length

BACKGROUND: Creation of human gene families was facilitated significantly by gene duplication and diversification. The (TG/CA)(n )repeats exhibit length variability, display genome-wide distribution, and are abundant in the human genome. Accumulation of evidences for their multiple functional roles including regulation of transcription and stimulation of recombination and splicing elect them as functional elements. Here, we report analysis of the distribution of (TG/CA)(n )repeats in human gene families. RESULTS: The 1,317 human gene families were classified into six functional classes. Distribution of (TG/CA)(n )repeats were analyzed both from a global perspective and from a stratified perspective based on their biological properties. The number of genes with repeats decreased with increasing repeat length and several genes (53%) had repeats of multiple types in various combinations. Repeats were positively associated with the class of Signaling and communication whereas, they were negatively associated with the classes of Immune and related functions and of Information. The proportion of genes with (TG/CA)(n )repeats in each class was proportional to the corresponding average gene length. The repeat distribution pattern in large gene families generally mirrored the global distribution pattern but differed particularly for Collagen gene family, which was rich in repeats. The position and flanking sequences of the repeats of Collagen genes showed high conservation in the Chimpanzee genome. However the majority of these repeats displayed length polymorphism. CONCLUSION: Positive association of repeats with genes of Signaling and communication points to their role in modulation of transcription. Negative association of repeats in genes of Information relates to the smaller gene length, higher expression and fundamental role in cellular physiology. In genes of Immune and related functions negative association of repeats perhaps relates to the smaller gene length and the directional nature of the recombinogenic processes to generate immune diversity. Thus, multiple factors including gene length, function and directionality of recombinogenic processes steered the observed distribution of (TG/CA)(n )repeats. Furthermore, the distribution of repeat patterns is consistent with the current model that long repeats tend to contract more than expand whereas, the reverse dynamics operates in short repeats