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This lecture covers the role of telomeres in cancer biology, focusing on telomerase, telomere replication problems, and the alternative lengthening of telomeres (ALT) pathway. It discusses historical perspectives, telomere function, end replication problems, telomerase structure, and the telomerase reaction cycle. The lecture also explores telomeric DNA structures, telomerase recruitment to telomeres, and the implications of telomere shortening in tumorigenesis. Additionally, it delves into the ALT pathway, TERRA long noncoding RNA, and the functions of TERRA in telomere maintenance and cancer. The lecture concludes with insights into the immortalization and transformation of human cells through telomerase reactivation.