Telomere-Telomere Recombination Is an Efficient Bypass Pathway for Telomere Maintenance in Saccharomyces cerevisiae
Many Saccharomyces telomeres bear one or more copies of the repetitive Y′ element followed by ∼350 bp of telomerase-generated C1–3A/TG1–3 repeats. Although most cells lacking a gene required for the telomerase pathway die after 50 to 100 cell divisions, survivors arise spontaneously in such cultures. These survivors have one of two distinct patterns of telomeric DNA (V. Lundblad and E. H. Blackburn, Cell 73:347–360, 1993). The more common of the two patterns, seen in type I survivors, is tandem amplification of Y′ followed by very short tracts of C1–3A/TG1–3 DNA. By determining the structure of singly tagged telomeres, chromosomes in type II survivors were shown to end in very long and heterogeneous-length tracts of C1–3A/TG1–3 DNA, with some telomeres having 12 kb or more of C1–3A/TG1–3 repeats. Maintenance of these long telomeres required the continuous presence of Rad52p. Whereas type I survivors often converted to the type II structure of telomeric DNA, the type II pattern was maintained for at least 250 cell divisions. However, during outgrowth, the structure of type II telomeres was dynamic, displaying gradual shortening as well as other structural changes that could be explained by continuous gene conversion events with other telomeres. Although most type II survivors had a growth rate similar to that of telomerase-proficient cells, their telomeres slowly returned to wild-type lengths when telomerase was reintroduced. The very long and heterogeneous-length telomeres characteristic of type II survivors in Saccharomyces are reminiscent of the telomeres in immortal human cell lines and tumors that maintain telomeric DNA in the absence of telomerase.
V(D)J recombination defects in lymphocytes due to RAG mutations: severe immunodeficiency with a spectrum of clinical presentations.
Severe combined immunodeficiency (SCID) comprises a heterogeneous group of primary immunodeficiencies, a proportion of which are due to mutations in either of the 2 recombination activating genes (RAG)-1 and -2, which mediate the process of V(D)J recombination leading to the assembly of antigen receptor genes. It is reported here that the clinical and immunologic phenotypes of patients bearing mutations in RAGs are more diverse than previously thought and that this variability is related, in part, to the specific type of RAG mutation. By analyzing 44 such patients from 41 families, the following conclusions were reached: (1) null mutations on both alleles lead to the T-B-SCID phenotype; (2) patients manifesting classic Omenn syndrome (OS) have missense mutations on at least one allele and maintain partial V(D)J recombination activity, which accounts for the generation of residual, oligoclonal T-lymphocytes; (3) in a third group of patients, findings were only partially compatible with OS, and these patients, who also carried at least one missense mutation, may be considered to have atypical SCID/OS; (4) patients with engraftment of maternal T cells as a complication of a transplacental transfusion represented a fourth group, and these patients, who often presented with a clinical phenotype mimicking OS, may be observed regardless of the type of RAG gene mutation. Analysis of the RAG genes by direct sequencing is an effective way to provide accurate diagnosis of RAG-deficient as opposed to RAG-independent V(D)J recombination defects, a distinction that cannot be made based on clinical and immunologic phenotype alone.
genetic algorithm positioning system process control sample size solar cell visible light dna sequence learning object indoor positioning received signal strength statistical process control indoor localization quantum dot statistical proces indoor positioning system count datum hecke algebra factorial design ieee standard binding site escherichia coli weighted moving average knowledge structure statistical quality control poisson structure cell cycle choice behavior econometric model quality level exponentially weighted moving fractional factorial design saccharomyces cerevisiae selection bia affine weyl group statistical process monitoring power conversion efficiency dye-sensitized solar cell charge transport uniform resource identifier learning object metadatum embryonic stem cell moving average control object class dye-sensitized solar reusable learning object linkage disequilibrium quantity discount spatial process spatial econometric population parameter embryonic stem reusable learning object metadatum heterojunction solar cell dna repair location fingerprinting cell development indoor positioning technique spatial econometric model radiation tolerance heterojunction solar genetic linkage signal peptide bulk heterojunction dna segment recombination rate bulk heterojunction solar dna recombination wifi-based indoor localization surface recombination escherichia coli. low-density lipoprotein indoor positioning solution proposed positioning system surface recombination velocity solar cells. neisseria meningitidi genetic heterogeneity learning object review dna break xrcc5 wt allele xrcc5 gene t cell receptor v(d)j recombination v(d)j recombination-activating protein 1 excretory function neuritis, autoimmune, experimental leukemia, b-cell dna sequence rearrangement immunoglobulin class switch recombination immunoglobulin class switching lipoprotein receptor dna breaks, double-stranded telomere maintenance v(d)j recombination genome encoded entity vdj recombinase recombination, genetic crossover (genetic algorithm) meiotic recombination homologous recombination