Fanconi anemia (FA) binding protein FAAP20 stabilizes FA complementation group A (FANCA) and participates in interstrand cross-link repair
Copyright policy )Fanconi anemia (FA) binding protein FAAP20 stabilizes FA complementation group A (FANCA) and participates in interstrand cross-link repair
The Fanconi anemia (FA) pathway participates in interstrand cross-link (ICL) repair and the maintenance of genomic stability. The FA core complex consists of eight FA proteins and two Fanconi anemia-associated proteins (FAAP24 and FAAP100). The FA core complex has ubiquitin ligase activity responsible for monoubiquitination of the FANCI-FANCD2 (ID) complex, which in turn initiates a cascade of biochemical events that allow processing and removal of cross-linked DNA and thereby promotes cell survival following DNA damage. Here, we report the identification of a unique component of the FA core complex, namely, FAAP20, which contains a RAD18-like ubiquitin-binding zinc-finger domain. Our data suggest that FAAP20 promotes the functional integrity of the FA core complex via its direct interaction with the FA gene product, FANCA. Indeed, somatic knockout cells devoid of FAAP20 displayed the hallmarks of FA cells, including hypersensitivity to DNA cross-linking agents, chromosome aberrations, and reduced FANCD2 monoubiquitination. Taking these data together, our study indicates that FAAP20 is an important player involved in the FA pathway.
- The University of Texas MD Anderson Cancer Center United States
- University of Hong Kong China (People's Republic of)
- University of Hong Kong (香港大學) China (People's Republic of)
Protein Structure, DNA Repair, Mitomycin, Ubiquitin - Chemistry, Molecular Sequence Data, Sequence Homology, 612, Dna Repair, Humans, Fanconi Anemia Complementation Group Proteins - Metabolism, Amino Acid Sequence, Chromosome Aberrations, Mitomycin - Chemistry, Fanconi Anemia Complementation Group A Protein, Sequence Homology, Amino Acid, Ubiquitin, Zinc Fingers, Fanconi Anemia Complementation Group Proteins, Protein Structure, Tertiary, Amino Acid, Cross-Linking Reagents, Fanconi Anemia, HEK293 Cells, Mutation, Hek293 Cells, Cross-Linking Reagents - Chemistry, Fanconi Anemia Complementation Group A Protein - Metabolism, Tertiary, Fanconi Anemia - Metabolism, Gene Deletion, Protein Binding
Protein Structure, DNA Repair, Mitomycin, Ubiquitin - Chemistry, Molecular Sequence Data, Sequence Homology, 612, Dna Repair, Humans, Fanconi Anemia Complementation Group Proteins - Metabolism, Amino Acid Sequence, Chromosome Aberrations, Mitomycin - Chemistry, Fanconi Anemia Complementation Group A Protein, Sequence Homology, Amino Acid, Ubiquitin, Zinc Fingers, Fanconi Anemia Complementation Group Proteins, Protein Structure, Tertiary, Amino Acid, Cross-Linking Reagents, Fanconi Anemia, HEK293 Cells, Mutation, Hek293 Cells, Cross-Linking Reagents - Chemistry, Fanconi Anemia Complementation Group A Protein - Metabolism, Tertiary, Fanconi Anemia - Metabolism, Gene Deletion, Protein Binding
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).75 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 10% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 1%
Citations provided by BIP!Popularity provided by BIP!