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Repeat Regions (repeat + regions)

Distribution by Scientific Domains

Life Sciences	50%

Selected Abstracts

In vitro expansion of DNA triplet repeats with bulge binders and different DNA polymerases

FEBS JOURNAL, Issue 18 2008
Di Ouyang
The expansion of DNA repeat sequences is associated with many genetic diseases in humans. Simple bulge DNA structures have been implicated as intermediates in DNA slippage within the DNA repeat regions. To probe the possible role of bulged structures in DNA slippage, we designed and synthesized a pair of simple chiral spirocyclic compounds [Xi Z, Ouyang D & Mu HT (2006) Bioorg Med Chem Lett16, 1180,1184], DDI-1A and DDI-1B, which mimic the molecular architecture of the enediyne antitumor antibiotic neocarzinostatin chromophore. Both compounds strongly stimulated slippage in various DNA repeats in vitro. Enhanced slippage synthesis was found to be synchronous for primer and template. CD spectra and UV thermal stability studies supported the idea that DDI-1A and DDI-1B exhibited selective binding to the DNA bulge and induced a significant conformational change in bulge DNA. The proposed mechanism for the observed in vitro expansion of long DNA is discussed. [source]

Mutations in the ataxia telangiectasia and rad3-related,checkpoint kinase 1 DNA damage response axis in colon cancers

GENES, CHROMOSOMES AND CANCER, Issue 12 2007
Kriste A. Lewis
In response to certain types of DNA damage, ataxia telangiectasia and rad3-related (ATR) phosphorylates checkpoint kinase 1 (CHEK1) resulting in cell cycle arrest and subsequent DNA repair. ATR and CHEK1 contain mononucleotide microsatellite repeat regions, which are mutational targets in tumors with defective mismatch repair (MMR). This study examined the frequency of such mutations in colon cancers and their impact on biologic behavior. Screening for ATR mutations in 48 tumors was performed using denaturing high-performance liquid chromatography (DHPLC) and confirmed with sequencing analysis. The CHEK1 exon 7 A(9) region was sequenced in 20 of the 27 (74%) tumors with high frequency of microsatellite instability (MSI-H). Univariate and multivariate analyses were used to examine associations with clinical outcomes. Frequent mutations in MSI-H colon cancers were identified within the ATR (37%)/CHEK1(5%) damage response pathway. Stage and MSI status both independently predicted overall survival (OS) and disease-free survival (DFS). ATR status was not associated with stage, but was associated with a trend toward improved DFS: 0/9 cancers recurred in MSI-H cases harboring ATR mutations vs. 4/18 recurrences in MSI-H cases without ATR mutations. This suggests that ATR mutations may affect clinical behavior and response to therapy in MSI-H colon cancers. © 2007 Wiley-Liss, Inc. [source]

Development and characterization of polymorphic markers for the sap-stain fungus Ophiostoma quercus

MOLECULAR ECOLOGY RESOURCES, Issue 1 2009
J. W. GROBBELAAR
Abstract Eight polymorphic markers were developed from South African isolates of Ophiostoma quercus. The genome was screened for repeat regions using the fast isolation by amplified fragment length polymorphism of sequences containing repeats protocol and 20 de novo primer pairs flanking putative microsatellite regions were designed. Eight loci were optimized and their polymorphisms evaluated by sequencing. The repeat and flanking regions were highly polymorphic containing both indels and base-pair substitutions revealing a total of 46 alleles in 14 isolates and an average heterozygosity of 0.68. Substantial sequence variability makes these markers useful for genotyping populations in order to calculate diversity and monitor global movement of O. quercus. [source]

Differential Antibody Recognition of Four Allelic Variants of the Merozoite Surface Protein-2 (MSP-2) of Plasmodium falciparum

THE JOURNAL OF EUKARYOTIC MICROBIOLOGY, Issue 5 2001
RENATA TONHOSOLO
ABSTRACT. The merozoite surface protein-2 (MSP-2) is a major vaccine candidate for the asexual blood stage of Plasmodium falciparum. MSP-2 is essentially dimorphic, and allelic families are named after the representative isolates FC27 and IC1. The polymorphic central region contains immunodominant repeats, which vary in number, length, and sequence within and between allelic families. We have examined the antibody recognition of repeat regions from both MSP-2 allelic families expressed as recombinant fusion peptides. The results are summarized as follows. (1) Immunization of mice with the fusion peptides elicited IgG antibodies that cross-reacted with the native MSP-2 molecule in an allelic family-specific manner. (2) These mouse antibodies recognized the recombinant proteins in both a variant-specific and a family-specific manner, as shown in inhibition immunoassays. Antibodies raised against the peptide FC27 seemed to be essentially variant-specific, since the soluble form of the S20 antigen (a member of FC27 family) had relatively little inhibitory effect on them. (3) The overall pattern of human IgG antibody responses to MSP-2 in Karitiana Indians, a population continuously exposed to hypoendemic malaria in the Brazilian Amazon Region, differs from that described in hyperendemic areas in Africa and Papua New Guinea in two important features: there was no clear age-dependent increase in the prevalence and mean concentration of specific IgG antibodies, and there was no skewing towards the IgG, subclass in antibody responses. (4) The relatively poor correlation between concentrations of IgG antibodies that are specific for members of the same allelic family suggests that recognition of MSP-2 peptides by naturally acquired antibodies was largely variant-specific in this population. The potential role of naturally acquired variant-specific antibodies in immune evasion, by selecting mutant parasites carrying insertions or deletions of repeat sequences, is briefly discussed. [source]