Arsenite Binds to the RING Finger Domain of FANCL E3 Ubiquitin Ligase and Inhibits DNA Interstrand Cross-link Repair

摘要

Arsenite, a widespread environmental contaminant, is highly toxic to living organisms. The molecular mechanisms underlying arsenic carcinogenesis, however, remains unclear. Since As(III) has been observed to bind to zinc finger motifs of some proteins, herein we employed several biological approaches and mass spectrometic analysis to demonstrate that As(III) can also coordinate with the zinc finger motif of FANCL to perturb its E3 ligase function, which suppresses the ubiquitination of FANCD2 and inhibits DNA interstrand cross-link (ICL) repair.