Monoubiquitination of the Fanconi anaemia protein FANCD2 is a key event leading 
to repair of interstrand cross-links. It was reported earlier that FANCD2 
co-localizes with NBS1. However, the functional connection between FANCD2 and 
MRE11 is poorly understood. In this study, we show that inhibition of MRE11, 
NBS1 or RAD50 leads to a destabilization of FANCD2. FANCD2 accumulated from 
mid-S to G2 phase within sites containing single-stranded DNA (ssDNA) 
intermediates, or at sites of DNA damage, such as those created by restriction 
endonucleases and laser irradiation. Purified FANCD2, a ring-like particle by 
electron microscopy, preferentially bound ssDNA over various DNA substrates. 
Inhibition of MRE11 nuclease activity by Mirin decreased the number of FANCD2 
foci formed in vivo. We propose that FANCD2 binds to ssDNA arising from 
MRE11-processed DNA double-strand breaks. Our data establish MRN as a crucial 
regulator of FANCD2 stability and function in the DNA damage response.