FAAP100 is essential for activation of the Fanconi anemia-associated DNA damage response pathway
| Autor: | Zhijiang Yan, Detlev Schindler, Minoru Takata, Amom Ruhikanta Meetei, Maureen E. Hoatlin, Reinhard Kalb, Johan P. de Winter, Yutong Xue, Masamichi Ishiai, Kornelia Neveling, Weidong Wang, Annette L. Medhurst, Hans Joenje, Anneke B. Oostra, Abdullah Mahmood Ali, Chen Ling, Arleen D. Auerbach |
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| Rok vydání: | 2007 |
| Předmět: |
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Molecular congenital hereditary and neonatal diseases and abnormalities DNA damage Fanconi Anemia Complementation Group L Protein Oligonucleotides Biology Article General Biochemistry Genetics and Molecular Biology hemic and lymphatic diseases FANCD2 Humans Monoubiquitination FANCL FANCM Molecular Biology BRCA2 Protein General Immunology and Microbiology BRCA1 Protein General Neuroscience FAN1 DNA Helicases nutritional and metabolic diseases Molecular biology FANCA FANCB DNA-Binding Proteins Multiprotein Complexes RNA Interference DNA Damage HeLa Cells |
| Zdroj: | The EMBO Journal. 26:2104-2114 |
| ISSN: | 1460-2075 0261-4189 |
| DOI: | 10.1038/sj.emboj.7601666 |
| Popis: | The Fanconi anemia (FA) core complex plays a central role in the DNA damage response network involving breast cancer susceptibility gene products, BRCA1 and BRCA2. The complex consists of eight FA proteins, including a ubiquitin ligase (FANCL) and a DNA translocase (FANCM), and is essential for monoubiquitination of FANCD2 in response to DNA damage. Here, we report a novel component of this complex, termed FAAP100, which is essential for the stability of the core complex and directly interacts with FANCB and FANCL to form a stable subcomplex. Formation of this subcomplex protects each component from proteolytic degradation and also allows their coregulation by FANCA and FANCM during nuclear localization. Using siRNA depletion and gene knockout techniques, we show that FAAP100-deficient cells display hallmark features of FA cells, including defective FANCD2 monoubiquitination, hypersensitivity to DNA crosslinking agents, and genomic instability. Our study identifies FAAP100 as a new critical component of the FA-BRCA DNA damage response network. |
| Databáze: | OpenAIRE |
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