Deregulated origin licensing leads to chromosomal breaks by rereplication of a gapped DNA template
| Autor: | J. Julian Blow, Raquel Herrador, Kai J. Neelsen, Kevin D. Creavin, Sofija Mijic, Isabella M.Y. Zanini, Massimo Lopes, Ralph Zellweger, Arnab Ray Chaudhuri |
|---|---|
| Přispěvatelé: | University of Zurich, Lopes, Massimo |
| Jazyk: | angličtina |
| Rok vydání: | 2013 |
| Předmět: |
DNA Replication
DNA re-replication Replication fork reversal Origin licensing Rereplication Cell Cycle Proteins Replication Origin Eukaryotic DNA replication Pre-replication complex DNA replication Genome Integrity Tumorigenesis Cell Line 1309 Developmental Biology DNA replication factor CDT1 Research Communication 03 medical and health sciences 0302 clinical medicine 1311 Genetics Genetics Humans RNA Small Interfering Replication protein A 030304 developmental biology 0303 health sciences biology F-Box Proteins 10061 Institute of Molecular Cancer Research Chromosome Breakage DNA Templates Genetic Licensing factor 030220 oncology & carcinogenesis biology.protein 570 Life sciences Origin recognition complex Developmental Biology |
| Zdroj: | Genes & Development, 27 (23) Genes & development |
| ISSN: | 0890-9369 1549-5477 |
| Popis: | Deregulated origin licensing and rereplication promote genome instability and tumorigenesis by largely elusive mechanisms. Investigating the consequences of Early mitotic inhibitor 1 (Emi1) depletion in human cells, previously associated with rereplication, we show by DNA fiber labeling that origin reactivation occurs rapidly, well before accumulation of cells with >4N DNA, and is associated with checkpoint-blind ssDNA gaps and replication fork reversal. Massive RPA chromatin loading, formation of small chromosomal fragments, and checkpoint activation occur only later, once cells complete bulk DNA replication. We propose that deregulated origin firing leads to undetected discontinuities on newly replicated DNA, which ultimately cause breakage of rereplicating forks. Genes & Development, 27 (23) ISSN:0890-9369 ISSN:1549-5477 |
| Databáze: | OpenAIRE |
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