Holliday Junctions Formed from Human Telomeric DNA
| Autor: | Arvind Ramanathan, Pengfei Li, Soraia Khiali, Deeksha Munnur, Gary N. Parkinson, Shozeb Haider |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
Models
Molecular 0301 basic medicine Genome instability Telomerase Biochemistry Catalysis 03 medical and health sciences chemistry.chemical_compound Colloid and Surface Chemistry Holliday junction Humans Nucleotide chemistry.chemical_classification DNA General Chemistry Telomere Cell biology enzymes and coenzymes (carbohydrates) 030104 developmental biology chemistry Nucleic Acid Conformation Crystallization Homologous recombination Recombination |
| Zdroj: | Journal of the American Chemical Society. 140:15366-15374 |
| ISSN: | 1520-5126 0002-7863 |
| DOI: | 10.1021/jacs.8b08699 |
| Popis: | Cells have evolved inherent mechanisms, like homologous recombination (HR), to repair damaged DNA. However, repairs at telomeres can lead to genomic instability, often associated with cancer. While most rapidly dividing cells employ telomerase, the others maintain telomere length through HR-dependent alternative lengthening of telomeres (ALT) pathways. Here we describe the crystal structures of Holliday junction intermediates of the HR-dependent ALT mechanism. Using an extended human telomeric repeat, we also report the crystal structure of two Holliday junctions in close proximity, which associate together through strand exchange to form a hemicatenated double Holliday junction. Our combined structural results demonstrate that ACC nucleotides in the C-rich lagging strand (5'-CTAACCCTAA-3') at the telomere repeat sequence constitute a conserved structural feature that constrains crossover geometry and is a preferred site for Holliday junction formation in telomeres. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|