The FANCD2–FANCI complex is recruited to DNA interstrand crosslinks before monoubiquitination of FANCD2

Chih-Chao Liang, Zhuolun Li, David Lopez-Martinez, William V. Nicholson, Catherine Vénien-Bryan and Martin A. Cohn ()
Additional contact information
Chih-Chao Liang: University of Oxford
Zhuolun Li: Institute of Mineralogy, Materials Physics and Cosmochemistry, UMR 7590, UPMC, CNRS, IRD, MNHN
David Lopez-Martinez: University of Oxford
William V. Nicholson: University of Oxford
Catherine Vénien-Bryan: Institute of Mineralogy, Materials Physics and Cosmochemistry, UMR 7590, UPMC, CNRS, IRD, MNHN
Martin A. Cohn: University of Oxford

Nature Communications, 2016, vol. 7, issue 1, 1-10

Abstract: Abstract The Fanconi anaemia (FA) pathway is important for the repair of DNA interstrand crosslinks (ICL). The FANCD2–FANCI complex is central to the pathway, and localizes to ICLs dependent on its monoubiquitination. It has remained elusive whether the complex is recruited before or after the critical monoubiquitination. Here, we report the first structural insight into the human FANCD2–FANCI complex by obtaining the cryo-EM structure. The complex contains an inner cavity, large enough to accommodate a double-stranded DNA helix, as well as a protruding Tower domain. Disease-causing mutations in the Tower domain are observed in several FA patients. Our work reveals that recruitment of the complex to a stalled replication fork serves as the trigger for the activating monoubiquitination event. Taken together, our results uncover the mechanism of how the FANCD2–FANCI complex activates the FA pathway, and explains the underlying molecular defect in FA patients with mutations in the Tower domain.

Date: 2016
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/ncomms12124 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms12124

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/ncomms12124

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().