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Science 333 (6040): 312-316

Copyright © 2011 by the American Association for the Advancement of Science

Structure of the FANCI-FANCD2 Complex: Insights into the Fanconi Anemia DNA Repair Pathway

Woo Joo,1,* Guozhou Xu,2,* Nicole S. Persky,1,3,* Agata Smogorzewska,4,5 Derek G. Rudge,1,3 Olga Buzovetsky,1,3 Stephen J. Elledge,3,4 Nikola P. Pavletich1,3,{dagger}

Abstract: Fanconi anemia is a cancer predisposition syndrome caused by defects in the repair of DNA interstrand cross-links (ICLs). Central to this pathway is the Fanconi anemia I–Fanconi anemia D2 (FANCI-FANCD2) (ID) complex, which is activated by DNA damage–induced phosphorylation and monoubiquitination. The 3.4 angstrom crystal structure of the ~300 kilodalton ID complex reveals that monoubiquitination and regulatory phosphorylation sites map to the I-D interface, suggesting that they occur on monomeric proteins or an opened-up complex and that they may serve to stabilize I-D heterodimerization. The 7.8 angstrom electron-density map of FANCI-DNA crystals and in vitro data show that each protein has binding sites for both single- and double-stranded DNA, suggesting that the ID complex recognizes DNA structures that result from the encounter of replication forks with an ICL.

1 Structural Biology Program, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
2 Sloan-Kettering Division, Joan and Sanford I. Weill Graduate School of Medical Sciences, Cornell University, New York, NY 10065, USA.
3 Howard Hughes Medical Institute, Memorial Sloan-Kettering Cancer Center, New York, NY 10065, USA.
4 Department of Genetics, Harvard Medical School, Division of Genetics, Brigham and Women’s Hospital, Boston, MA 02115, USA.
5 Laboratory of Genome Maintenance, The Rockefeller University, New York, NY 10065, USA.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: pavletin{at}

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