Telomeres and telomerase in human hematologic neoplasia.
Telomeres are the physical ends of eukaryotic chromosomes. Telomeric DNA sequences are highly conserved in all well-characterized eukaryotic nuclear chromosomes and differ greatly from the termini of linear viral, extranuclear plasmid, or mitochondrial DNA. Human telomeric DNA consists of 2-15 kb of a tandemly repeated sequence (TTAGGG)n, oriented 5'-3' toward the end of the chromosome. The evolutionary conservation of this repetitive DNA sequence implies that the sequence is essential to cellular function. These repeated sequences are synthesized by an RNA-dependent DNA polymerase, telomerase, which is composed of an essential RNA and a few proteins. Human telomerase has been proposed to be repressed in somatic tissues, and human telomeres become shorter during somatic development and with increasing age. Telomeres in tumors are even shorter, and loss of telomeric DNA during tumorigenesis may contribute to the genome instability associated with transformed cells. This article reviews the structure and function of telomeres and the recent studies on human hematologic cells.
Yamada
O
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Department of Hematology, Tokyo Women's Medical College, Japan.
D000818:Animals; D001483:Base Sequence; D001773:Blood Cells / Q000648:ultrastructure; D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D016922:Cellular Senescence / Q000235:genetics; D002877:Chromosomes, Human / Q000235:genetics / Q000648:ultrastructure*; D004261:DNA Replication; D004268:DNA-Binding Proteins / Q000502:physiology; D005057:Eukaryotic Cells / Q000502:physiology / Q000648:ultrastructure; D019337:Hematologic Neoplasms / Q000201:enzymology / Q000235:genetics*; D006412:Hematopoietic Stem Cells / Q000648:ultrastructure; D006801:Humans; D007938:Leukemia / Q000201:enzymology / Q000209:etiology / Q000235:genetics / Q000473:pathology; D009363:Neoplasm Proteins / Q000502:physiology*; D014411:Neoplastic Stem Cells / Q000648:ultrastructure; D012313:RNA / Q000235:genetics / Q000502:physiology; D012091:Repetitive Sequences, Nucleic Acid; D019098:Telomerase / Q000502:physiology*; D016615:Telomere / Q000502:physiology / Q000648:ultrastructure; D013698:Templates, Genetic
D004268:DNA-Binding Proteins; D009363:Neoplasm Proteins; D012313:RNA; D019098:Telomerase