Long G tails at both ends of human chromosomes suggest a C strand degradation mechanism for telomere shortening.
The chromosomes of lower eukaryotes have short telomeric 3' extensions. Using a primer-extension/nick-translation technique and nondenaturing hybridization, we find long 3' G-rich tails at human chromosome ends in mortal primary fibroblasts, umbilical vein endothelial cells, and leukocytes, as well as in immortalized fibroblasts. For all cells tested, >80% of the telomeres have long G-rich overhangs, averaging 130-210 bases in length, in disagreement with the conventional model for incomplete lagging-strand replication, which predicts overhangs on 50% of the chromosome ends. The observed G tails must exist during most of the cell cycle and probably result from degradation of both chromosome ends. The average lengths of the G tails are quantitatively consistent with the observed rates of human chromosome shortening.
Makarov
V L
VL
Biophysics Research Division, University of Michigan, Ann Arbor 48109-1055, USA.
Hirose
Y
Y
Langmore
J P
JP
D000468:Alkalies; D002461:Cell Line, Transformed; D002478:Cells, Cultured / Q000502:physiology; D002875:Chromosomes / Q000502:physiology*; D017931:DNA Primers; D004259:DNA-Directed DNA Polymerase; D004587:Electrophoresis, Agar Gel; D015180:Electrophoresis, Gel, Two-Dimensional; D005333:Fetus / Q000166:cytology; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D006147:Guanine / Q000032:analysis; D006801:Humans; D008168:Lung / Q000166:cytology; D009693:Nucleic Acid Hybridization; D012194:RNA-Directed DNA Polymerase; D019914:Taq Polymerase; D016615:Telomere / Q000235:genetics* / Q000378:metabolism*
D000468:Alkalies; D017931:DNA Primers; D006147:Guanine; D019914:Taq Polymerase; D012194:RNA-Directed DNA Polymerase; D004259:DNA-Directed DNA Polymerase