Abstract
Using a combination of different oligonucleotides and restriction enzymes we have examined the gross organisation of repeats within the most distal region of human chromosomes. We demonstrate here that human telomeres do not contain a pure uniform 6 base pair repeat unit but that there are at least three types of repeat. These three types of repeat are present at the ends of most or all human chromosomes. The distribution of each type of repeat appears to be non-random. Each human telomere has a similar arrangement of these repeats relative to the ends of the chromosome. This could reflect differences in the functions that they perform, or might result from the mutation and correction processes occurring at human telomeres. The number of repeat units, the repeat types and arrangement differs at mouse telomeres. Analysing the change in length of the telomeric repeat region between an individuals blood and germline DNA reveals that this is due to variable amounts of the TTAGGG repeat and not the other repeat types. This organization of repeat units at human telomeres will only be confirmed upon the isolation and sequencing of full length (10-15 kb), intact human telomeres.
MeSH Terms
Animals
Autoradiography
Base Composition
Binding, Competitive
Chromosomes, Human
Cold Temperature
Deoxyribonucleases, Type II Site-Specific
Endodeoxyribonucleases
Guanine
Humans
Mice
Nucleic Acid Hybridization
Oligonucleotide Probes
Plants/genetics
Plasmodium berghei/genetics
Plasmodium falciparum/genetics
Repetitive Sequences, Nucleic Acid
Restriction Mapping
Tetrahymena/genetics
Trypanosoma brucei brucei/genetics
Chemicals
Oligonucleotide Probes
Guanine
Endodeoxyribonucleases
exonuclease Bal 31
endodeoxyribonuclease MnlI
Deoxyribonucleases, Type II Site-Specific
GGTGA-specific type II deoxyribonucleases
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Allshire R C
MRC Human Genetics Unit, Western General Hospital, Edinburgh, UK.
Dempster M
Hastie N D
References (32)
32 references, click to expand
-
Base sequence and evolution of guinea-pig alpha-satellite DNA.
Nature. 1970 Aug 22;227(5260):794-8
PMID: 4317352
-
Molecular cloning of human telomeres in yeast.
Nature. 1989 Apr 27;338(6218):774-6
PMID: 2541342
-
Similarity of satilite DNA properties in the order Rodentia.
Nucleic Acids Res. 1977 Sep;4(9):3215-27
PMID: 561953
-
Nucleotide sequences of HS-alpha satellite DNA from kangaroo rat Dipodomys ordii and characterization of similar sequences in other rodents.
Cell. 1977 Dec;12(4):1069-84
PMID: 597857
-
An intervening sequence in the gene coding for 25S ribosomal RNA of Tetrahymena pigmentosa.
Cell. 1979 Mar;16(3):565-73
PMID: 455443
-
Is there left-handed DNA at the ends of yeast chromosomes?
Nature. 1983 Mar 3;302(5903):84-6
PMID: 6338397
-
Three-dimensional architecture of a polytene nucleus.
Nature. 1983 Apr 21;302(5910):676-81
PMID: 6403872
-
Sequence and hairpin structure of an inverted repeat series at termini of the Physarum extrachromosomal rDNA molecule.
Cell. 1983 Apr;32(4):1287-99
PMID: 6301691
-
Genomic sequencing.
Proc Natl Acad Sci U S A. 1984 Apr;81(7):1991-5
PMID: 6326095
-
The use of cloned Y chromosome-specific DNA probes for fetal sex determination in first trimester prenatal diagnosis.
Hum Genet. 1984;66(4):347-51
PMID: 6539298
-
DNA sequences of telomeres maintained in yeast.
Nature. 1984 Jul 12-18;310(5973):154-7
PMID: 6330571
-
The molecular structure of centromeres and telomeres.
Annu Rev Biochem. 1984;53:163-94
PMID: 6383193
-
Identification of a telomeric DNA sequence in Plasmodium berghei.
EMBO J. 1985 Nov;4(11):2991-5
PMID: 2998771
-
Identification of a specific telomere terminal transferase activity in Tetrahymena extracts.
Cell. 1985 Dec;43(2 Pt 1):405-13
PMID: 3907856
-
Automatic reading of DNA sequencing gel autoradiographs using a large format digital scanner.
Nucleic Acids Res. 1986 Jan 10;14(1):417-24
PMID: 3753777
-
Universal restriction endonucleases: designing novel cleavage specificities by combining adapter oligodeoxynucleotide and enzyme moieties.
Gene. 1985;40(2-3):169-73
PMID: 3007286
-
Telomeric site position heterogeneity in macronuclear DNA of Paramecium primaurelia.
Nucleic Acids Res. 1987 Feb 25;15(4):1717-28
PMID: 3029725
-
Restriction enzymes and their isoschizomers.
Nucleic Acids Res. 1987;15 Suppl:r189-217
PMID: 3033611
-
Variability at the telomeres of the human X/Y pseudoautosomal region.
Cold Spring Harb Symp Quant Biol. 1986;51 Pt 1:213-9
PMID: 3034483
-
Dynamics of telomere length variation in Tetrahymena thermophila.
Cell. 1987 Jul 31;50(3):477-83
PMID: 3607876
-
Identification of the telomeric sequence of the acellular slime molds Didymium iridis and Physarum polycephalum.
Nucleic Acids Res. 1987 Nov 25;15(22):9143-52
PMID: 3684591
-
The telomere terminal transferase of Tetrahymena is a ribonucleoprotein enzyme with two kinds of primer specificity.
Cell. 1987 Dec 24;51(6):887-98
PMID: 3319189
-
Developmentally controlled telomere addition in wild-type and mutant paramecia.
Mol Cell Biol. 1988 Jan;8(1):251-8
PMID: 3336360
-
Generation of telomere-length heterogeneity in Saccharomyces cerevisiae.
Proc Natl Acad Sci U S A. 1988 Jan;85(2):534-8
PMID: 3277178
-
Isolation of a higher eukaryotic telomere from Arabidopsis thaliana.
Cell. 1988 Apr 8;53(1):127-36
PMID: 3349525
-
Telomeric repeat from T. thermophila cross hybridizes with human telomeres.
Nature. 1988 Apr 14;332(6165):656-9
PMID: 2833706
-
Formation of parallel four-stranded complexes by guanine-rich motifs in DNA and its implications for meiosis.
Nature. 1988 Jul 28;334(6180):364-6
PMID: 3393228
-
A highly conserved repetitive DNA sequence, (TTAGGG)n, present at the telomeres of human chromosomes.
Proc Natl Acad Sci U S A. 1988 Sep;85(18):6622-6
PMID: 3413114
-
A telomeric sequence in the RNA of Tetrahymena telomerase required for telomere repeat synthesis.
Nature. 1989 Jan 26;337(6205):331-7
PMID: 2463488
-
Recombination occurs during telomere formation in yeast.
Nature. 1989 Feb 2;337(6206):429-33
PMID: 2536898
-
Cloning of human telomeres by complementation in yeast.
Nature. 1989 Apr 27;338(6218):771-4
PMID: 2541341
-
Isolation of high-molecular-weight DNA from mammalian cells.
Eur J Biochem. 1973 Jul 2;36(1):32-8
PMID: 4200179