The vertebrate Hef ortholog is a component of the Fanconi anemia tumor-suppressor pathway
| Autor: | Arno F. Alpi, Georgina Mosedale, Frederic Langevin, Mark S. Johnson, Paul E. Pace, Wojciech Niedzwiedz, Ketan J. Patel, José B. Pereira-Leal, Franco Perrina |
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| Rok vydání: | 2005 |
| Předmět: |
DNA Replication
DNA Repair DNA repair Cell Cycle Proteins Biology Protein degradation Genomic Instability Cell Line Avian Proteins Evolution Molecular Structural Biology FANCD2 Animals Humans FANCM Molecular Biology Gene Conserved Sequence Adenosine Triphosphatases Genetics Tumor Suppressor Proteins FAN1 Fanconi Anemia Complementation Group C Protein DNA Helicases DNA replication Nuclear Proteins DNA Endonucleases Fanconi Anemia Complementation Group Proteins Chromatin Cell biology DNA-Binding Proteins Fanconi Anemia Chickens DNA Damage |
| Zdroj: | Nature Structural & Molecular Biology. 12:763-771 |
| ISSN: | 1545-9985 1545-9993 |
| DOI: | 10.1038/nsmb981 |
| Popis: | The helicase-associated endonuclease for fork-structured DNA (Hef) is an archaeabacterial protein that processes blocked replication forks. Here we have isolated the vertebrate Hef ortholog and investigated its molecular function. Disruption of this gene in chicken DT40 cells results in genomic instability and sensitivity to DNA cross-links. The similarity of this phenotype to that of cells lacking the Fanconi anemia-related (FA) tumor-suppressor genes led us to investigate whether Hef functions in this pathway. Indeed, we found a genetic interaction between the FANCC and Hef genes. In addition, Hef is a component of the FA nuclear protein complex that facilitates its DNA damage-inducible chromatin localization and the monoubiquitination of the FA protein FANCD2. Notably, Hef interacts directly with DNA structures that are intermediates in DNA replication. This discovery sheds light on the origins, regulation and molecular function of the FA tumor-suppressor pathway in the maintenance of genome stability. © 2005 Nature Publishing Group. |
| Databáze: | OpenAIRE |
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