J Korean Soc Pediatr Nephrol.  2008 Apr;12(1):11-22.

Kidneys with bad ends

Affiliations
  • 1Department of Biochemistry, College of Medicine, Pochun CHA University, Bungdang, Korea. dcsuh@hanmail.net

Abstract

Telomeres consist of tandem guanine-thymine(G-T) repeats in most eukaryotic chromosomes. Human telomeres are predominantly linear, double stranded DNA as they ended in 30-200 nucleotides(bases,b) 3'-overhangs. In DNA replication, removal of the terminal RNA primer from the lagging strand results in a 3'-overhang of uncopied DNA. This is because of bidirectional DNA replication and specificity of unidirectional DNA polymerase. After the replication, parental and daughter DNA strands have unequal lengths due to a combination of the end- replication problem and end-processing events. The gradual chromosome shortening is observed in most somatic cells and eventually leads to cellular senescence. Telomere shortening could be a molecular clock that signals the replicative senescence. The shortening of telomeric ends of human chromosomes, leading to sudden growth arrest, triggers DNA instability as biological switches. In addition, telomere dysfunction may cause chronic allograft nephropathy or kidney cancers. The renal cell carcinoma(RCC) in women may be less aggressive and have less genomic instability than in man. Younger patients with telomere dysfunction are at a higher risk for RCC than older patients. Thus, telomeres maintain the integrity of the genome and are involved in cellular aging and cancer. By studying the telomeric DNA, we may characterize the genetic determinants in diseases and discover the tools in molecular medicine.

Keyword

Telomeres; Kidneys; Senescence

MeSH Terms

Aging
Cell Aging
Chromosomes, Human
DNA
DNA Replication
Female
Genome
Genomic Instability
Humans
Kidney
Kidney Neoplasms
Molecular Medicine
Nuclear Family
Parents
RNA
Sensitivity and Specificity
Telomere
Telomere Shortening
Transplantation, Homologous
DNA
RNA
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