Structure and Variability of Human Chromosome Ends

Structure and Variability of Human Chromosome Ends

Feb. 1990 | TITIA DE LANGE,1†*, LILY SHUIE,1 RICHARD M. MYERS2,3 DAVID R. COX,2,4 SUSAN L. NAYLOR,5 ANN M. KILLERY,6 AND HAROLD E. VARMUS1,2
The article "Structure and Variability of Human Chromosome Ends" explores the composition and variability of human chromosome ends, focusing on telomeres and subtelomeric regions. Telomeres are specialized structures at the ends of chromosomes composed of repetitive TTAGGG sequences. The study describes a method for directly cloning telomere-associated DNA, revealing that human chromosomes end in a long region of TTAGGG repeats, which can be up to 14 kb in length. This region is not conserved in rodent DNA and is part of a subtelomeric repeat that is present at 10 to 25% of human chromosome ends. These subtelomeric repeats show high variability and are subject to de novo methylation in somatic cells. The study also identifies that telomeres in somatic cells are shorter and more heterogeneous in length compared to those in sperm, and further shortening is observed in primary tumors, indicating telomere instability. The subtelomeric region extends beyond the TTAGGG repeats and contains sequences that are sensitive to BAL 31 nuclease, suggesting their proximity to chromosome ends. These sequences are not conserved in rodent DNA, making them useful for identifying human chromosomes in human-rodent hybrid cell lines. The research highlights the importance of telomeres in protecting chromosome ends and maintaining genomic stability. It also discusses the role of telomerase in elongating telomeres and the implications of telomere shortening in somatic cells. The study provides insights into the structure and variability of human chromosome ends, emphasizing the significance of telomere maintenance and the potential consequences of telomere loss in cellular aging and disease. The findings contribute to understanding the molecular mechanisms underlying chromosome stability and the evolution of telomere sequences across species.The article "Structure and Variability of Human Chromosome Ends" explores the composition and variability of human chromosome ends, focusing on telomeres and subtelomeric regions. Telomeres are specialized structures at the ends of chromosomes composed of repetitive TTAGGG sequences. The study describes a method for directly cloning telomere-associated DNA, revealing that human chromosomes end in a long region of TTAGGG repeats, which can be up to 14 kb in length. This region is not conserved in rodent DNA and is part of a subtelomeric repeat that is present at 10 to 25% of human chromosome ends. These subtelomeric repeats show high variability and are subject to de novo methylation in somatic cells. The study also identifies that telomeres in somatic cells are shorter and more heterogeneous in length compared to those in sperm, and further shortening is observed in primary tumors, indicating telomere instability. The subtelomeric region extends beyond the TTAGGG repeats and contains sequences that are sensitive to BAL 31 nuclease, suggesting their proximity to chromosome ends. These sequences are not conserved in rodent DNA, making them useful for identifying human chromosomes in human-rodent hybrid cell lines. The research highlights the importance of telomeres in protecting chromosome ends and maintaining genomic stability. It also discusses the role of telomerase in elongating telomeres and the implications of telomere shortening in somatic cells. The study provides insights into the structure and variability of human chromosome ends, emphasizing the significance of telomere maintenance and the potential consequences of telomere loss in cellular aging and disease. The findings contribute to understanding the molecular mechanisms underlying chromosome stability and the evolution of telomere sequences across species.
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Understanding Structure and variability of human chromosome ends