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- Title
FAAP100 is essential for activation of the Fanconi anemia-associated DNA damage response pathway.
- Authors
Ling, Chen; Ishiai, Masamichi; Ali, Abdullah Mahmood; Medhurst, Annette L; Neveling, Kornelia; Kalb, Reinhard; Yan, Zhijiang; Xue, Yutong; Oostra, Anneke B; Auerbach, Arleen D; Hoatlin, Maureen E; Schindler, Detlev; Joenje, Hans; de Winter, Johan P; Takata, Minoru; Meetei, Amom Ruhikanta; Wang, Weidong
- Abstract
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.
- Publication
The EMBO journal, 2007, Vol 26, Issue 8, p2104
- ISSN
0261-4189
- Publication type
Journal Article
- DOI
10.1038/sj.emboj.7601666