The human telomeric proteome during telomere replication
| Autor: | Alexandra Vancevska, Joachim Lingner, Chih-Yi Gabriela Lin, Anna Christina Naeger, Thomas Lunardi, Gérald Lossaint |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
DNA Replication
Telomerase strand synthesis AcademicSubjects/SCI00010 Telomere-Binding Proteins Biology Genome Shelterin Complex Histones dna-replication repeat-containing rna 03 medical and health sciences 0302 clinical medicine Histone H1 Replication (statistics) Genetics Humans trf1 Telomere Shortening 030304 developmental biology chromatin compaction Telomere-binding protein 0303 health sciences blm helicase Gene regulation Chromatin and Epigenetics DNA replication dynamics Telomere proteins Cell biology HEK293 Cells histone chaperone Proteome Replisome complex 030217 neurology & neurosurgery HeLa Cells |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 0305-1048 |
| Popis: | Telomere shortening can cause detrimental diseases and contribute to aging. It occurs due to the end replication problem in cells lacking telomerase. Furthermore, recent studies revealed that telomere shortening can be attributed to difficulties of the semi-conservative DNA replication machinery to replicate the bulk of telomeric DNA repeats. To investigate telomere replication in a comprehensive manner, we develop QTIP-iPOND - Quantitative Telomeric chromatin Isolation Protocol followed by isolation of Proteins On Nascent DNA - which enables purification of proteins that associate with telomeres specifically during replication. In addition to the core replisome, we identify a large number of proteins that specifically associate with telomere replication forks. Depletion of several of these proteins induces telomere fragility validating their importance for telomere replication. We also find that at telomere replication forks the single strand telomere binding protein POT1 is depleted, whereas histone H1 is enriched. Our work reveals the dynamic changes of the telomeric proteome during replication, providing a valuable resource of telomere replication proteins. To our knowledge, this is the first study that examines the replisome at a specific region of the genome. |
| Databáze: | OpenAIRE |
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