Healing of broken human chromosomes by the addition of telomeric repeats.
We have characterized and compared a series of naturally occurring chromosomal truncations involving the terminal region of the short arm of human chromosome 16 (16p13.3). All six broken chromosomes appear to have been stabilized by the direct addition of telomeric repeats (TTAGGG)n to nontelomeric DNA. In five of the six chromosomes, sequence analysis shows that the three of four nucleotides preceding the point of telomere addition are complementary to and in phase with the putative RNA template of human telomerase. Otherwise we have found no common structural features around the breakpoint regions. These findings, together with previously reported in vitro data, suggest that chromosome-healing events in man can be mediated by telomerase and that a small region of complementarity to the RNA template of telomerase at the end of a broken chromosome may be sufficient to prime healing in vivo.
Flint
J
J
Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford, England.
Craddock
C F
CF
Villegas
A
A
Bentley
D P
DP
Williams
H J
HJ
Galanello
R
R
Cao
A
A
Wood
W G
WG
Ayyub
H
H
Higgs
D R
DR
D001483:Base Sequence; D002872:Chromosome Deletion; D002885:Chromosomes, Human, Pair 16 / Q000201:enzymology* / Q000502:physiology*; D004253:DNA Nucleotidylexotransferase / Q000096:biosynthesis / Q000502:physiology*; D017931:DNA Primers; D004261:DNA Replication; D018076:DNA, Complementary / Q000378:metabolism; D005914:Globins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012313:RNA / Q000378:metabolism; D012091:Repetitive Sequences, Nucleic Acid; D013698:Templates, Genetic; D017085:alpha-Thalassemia / Q000235:genetics
D017931:DNA Primers; D018076:DNA, Complementary; D012313:RNA; D005914:Globins; D004253:DNA Nucleotidylexotransferase