Sept. 2002 | Yu-Sheng Cong, Woodring E. Wright, and Jerry W. Shay
The chapter discusses the functional assembly and regulation of human telomerase, a key enzyme involved in maintaining telomere length and cellular immortalization. Telomeres, protective structures at the ends of chromosomes, consist of tandem repeat DNA sequences and associated proteins. Telomerase, an RNA-dependent DNA polymerase, synthesizes telomeric DNA, allowing cells to maintain telomere length and avoid replicative senescence. The chapter highlights the importance of two core components of telomerase: the RNA component (hTR) and the catalytic protein component (hTERT). hTR provides the template for telomeric DNA synthesis, while hTERT catalyzes the synthesis. The assembly of functional telomerase involves multiple steps, including the interaction of hTR with hTERT and other associated proteins. The chapter also explores the regulation of telomerase activity, which occurs at various levels, including transcription, mRNA splicing, maturation, and subcellular localization. It discusses the role of transcription factors such as c-Myc, Sp1, and steroid hormones in activating hTERT transcription, and the involvement of negative regulators like Mad1 in repressing hTERT expression. The regulation of telomerase is crucial for understanding cellular aging, cancer development, and potential therapeutic strategies.The chapter discusses the functional assembly and regulation of human telomerase, a key enzyme involved in maintaining telomere length and cellular immortalization. Telomeres, protective structures at the ends of chromosomes, consist of tandem repeat DNA sequences and associated proteins. Telomerase, an RNA-dependent DNA polymerase, synthesizes telomeric DNA, allowing cells to maintain telomere length and avoid replicative senescence. The chapter highlights the importance of two core components of telomerase: the RNA component (hTR) and the catalytic protein component (hTERT). hTR provides the template for telomeric DNA synthesis, while hTERT catalyzes the synthesis. The assembly of functional telomerase involves multiple steps, including the interaction of hTR with hTERT and other associated proteins. The chapter also explores the regulation of telomerase activity, which occurs at various levels, including transcription, mRNA splicing, maturation, and subcellular localization. It discusses the role of transcription factors such as c-Myc, Sp1, and steroid hormones in activating hTERT transcription, and the involvement of negative regulators like Mad1 in repressing hTERT expression. The regulation of telomerase is crucial for understanding cellular aging, cancer development, and potential therapeutic strategies.