MRE11–RAD50–NBS1 is a critical regulator of FANCD2 stability and function during DNA double-strand break repair
AUTOR(ES)
Roques, Céline
FONTE
Nature Publishing Group
RESUMO
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.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=2735166Documentos Relacionados
- Reconstitution of the mammalian DNA double-strand break end-joining reaction reveals a requirement for an Mre11/Rad50/NBS1-containing fraction
- The Mre11-Rad50-Xrs2 Protein Complex Facilitates Homologous Recombination-Based Double-Strand Break Repair in Saccharomyces cerevisiae†
- Interaction of Mre11 and Rad50: Two Proteins Required for DNA Repair and Meiosis-Specific Double-Strand Break Formation in Saccharomyces Cerevisiae
- Modulation of Saccharomyces Cerevisiae DNA Double-Strand Break Repair by Srs2 and Rad51
- hMre11 and hRad50 nuclear foci are induced during the normal cellular response to DNA double-strand breaks.