Telomere Length, Aging, and Somatic Cell Turnover
The Journal of Experimental MedicinePublished 19 July 1999Open access
Richard J. Hodes
Citations110
SJR quartileQ1
SJR score5.83
SNIP1.99
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TL;DR
Telomeres are unique protein–DNA structures that comprise the termini of eukaryotic linear chromosomes that consist of G-rich hexanucleotide repeats that in vertebrate cells areTTAGGG.
Abstract
Telomeres are unique protein–DNA structures that comprise the termini of eukaryotic linear chromosomes (for review see references ([1][1]), ([2][2])). Telomeric DNA does not contain protein-encoding genes but rather consists of G-rich hexanucleotide repeats that in vertebrate cells are (TTAGGG)n
Keywords
MedicineBiochemistry, Genetics and Molecular Biology
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PubMedLoss of telomeric DNA during aging of normal and trisomy 21 human lymphocytes.
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