Genetic and physical interactions between the yeastELG1gene and orthologs of the Fanconi anemia pathway
| العنوان: | Genetic and physical interactions between the yeastELG1gene and orthologs of the Fanconi anemia pathway |
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| المؤلفون: | Martin Kupiec, Keren Shemesh, Batia Liefshitz, Shivani Singh |
| المصدر: | Cell Cycle |
| بيانات النشر: | Informa UK Limited, 2013. |
| سنة النشر: | 2013 |
| مصطلحات موضوعية: | Genome instability, Saccharomyces cerevisiae Proteins, Chromosomal Proteins, Non-Histone, Saccharomyces cerevisiae, Mutant, Elg1, CHL1, DEAD-box RNA Helicases, Fanconi anemia, Report, Proliferating Cell Nuclear Antigen, Two-Hybrid System Techniques, medicine, PCNA, Humans, Hydroxyurea, FANCM, Molecular Biology, Gene, Genetics, biology, Sumoylation, Helicase, Cell Biology, Methyl Methanesulfonate, biology.organism_classification, medicine.disease, Fanconi Anemia, Mutation, biology.protein, DNA damage, Carrier Proteins, genome stability, Developmental Biology |
| الوصف: | Fanconi anemia (FA) is a human syndrome characterized by genomic instability and increased incidence of cancer. FA is a genetically heterogeneous disease caused by mutations in at least 15 different genes; several of these genes are conserved in the yeast Saccharomyces cerevisiae. Elg1 is also a conserved protein that forms an RFC-like complex, which interacts with SUMOylated PCNA. The mammalian Elg1 protein has been recently found to interact with the FA complex. Here we analyze the genetic interactions between elg1Δ and mutants of the yeast FA-like pathway. We show that Elg1 physically contacts the Mhf1/Mhf2 histone-like complex and genetically interacts with MPH1 (ortholog of the FANCM helicase) and CHL1 (ortholog of the FANCJ helicase) genes. We analyze the sensitivity of double, triple, quadruple and quintuple mutants to methylmethane sulfonate (MMS) and to hydroxyurea (HU). Our results show that genetic interactions depend on the type of DNA damaging agent used and show a hierarchy: Chl1 and Elg1 play major roles in the survival to these genotoxins and exhibit synthetic fitness reduction. Mph1 plays a lesser role, and the effect of the Mhf1/2 complex is seen only in the absence of Elg1 on HU-containing medium. Finally, we dissect the relationship between yeast FA-like mutants and the replication clamp, PCNA. Our results point to an intricate network of interactions rather than a single, linear repair pathway. |
| تدمد: | 1551-4005 1538-4101 |
| DOI: | 10.4161/cc.24756 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::fe95f680c703010c6079fdb53e8ec571 https://doi.org/10.4161/cc.24756 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....fe95f680c703010c6079fdb53e8ec571 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15514005 15384101 |
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| DOI: | 10.4161/cc.24756 |