第十一章 端粒端粒酶与肿瘤.pptVIP

第十一章 端粒、端粒酶与肿瘤 端粒 端粒酶 端粒、端粒酶与肿瘤 问题与展望 一、Telomere Telomeres are distinctive DNA-protein structures at the ends of linear chromosomes. （一）、structure Telomeric DNA Telomeric-associated proteins Telomeric DNA Highly repetitive:TTAGGG The length of the TTAGGG tracts varies greatly Telomere-associated proteins TRF1 and TRF2 TIN2 and hRAP1 Tankyrase(TANK1, TANK2) Ku Fig.1 The telomeric t loop Two states: A closed, protected form An open, unprotected form If no telomerase, cell may sense the open form as a dysfunctional telomere. The dysfunctional telomere may then signal a senescence arrest or cell death, depending on the integrity of genes that control and implement the senescence/telomere checkpoint. (二)、telomere length is regulated by cells and organisms In the germ cells Maintain telomere lengths within species-specific limits by the balanced action of the enzyme telomerase and a variety telomere-associated proteins In somatic cells The telomere repeats have been proposed to provide each cell with a counting mechanism that helps prevent the unlimited proliferetion of wayward cells in adult tissues. Our somatic cells are born with a full complement of telomeric repeats The telomerase enzyme is turned off in a tissue like the skin Each time a cell divides, it loses 50-100 nucleotides from each of its telomeres After many cell generations, the descendent cells will inherit defective chromosomes and consequently will withdraw permanently from the cell cycle and cease dividing— replicative cell senescence Telomere sequence may also be lost by exonuclease digestion and oxidative damage, unless mechanisms are in place to counter this loss The telomere shirk with each cell division Short telomeres can cause cellular senescence, cell death, or genomic instability, depending on the cell context (三)、 the end-replication problem DNA replication is bidirectional DNA polymerases are unidirectional DNA polymerases require a primer The lagging strand of the molecule is in