Journal article
FANCM Connects the Genome Instability Disorders Bloom's Syndrome and Fanconi Anemia
AJ Deans, SC West
Molecular Cell | Published : 2009
Abstract
Fanconi Anemia (FA) and Bloom's Syndrome (BS) are genetic disorders characterized by overlapping phenotypes, including aberrant DNA repair and cancer predisposition. Here, we show that the FANCM gene product, FANCM protein, links FA and BS by acting as a protein anchor and bridge that targets key components of the FA and BS pathways to stalled replication forks, thus linking multiple components that are necessary for efficient DNA repair. Two highly conserved protein:protein interaction motifs in FANCM, designated MM1 and MM2, were identified. MM1 interacts with the FA core complex by binding to FANCF, whereas MM2 interacts with RM1 and topoisomerase IIIα, components of the BS complex. The M..
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Awarded by Fanconi Anemia Research Fund
Funding Acknowledgements
We thank the Cell Services and Peptide Synthesis core facilities at CRUK for their help and members of our laboratory for discussions and reagents. We also thank Rachel Coulthard, Neil McDonald, Simon Boulton, and Spencer Collis (LRI); Ian Hickson (Oxford University); Yilun Liu (Yale University); K.J. Patel (LMB Cambridge); Johan de Winter (VU Medical Center); and the Fanconi Anemia Research Fund (Oregon) for kindly providing advice and reagents. A.J.D. is a recipient of a C.J. Martin postdoctoral fellowship from the National Health and Medical Research Council of Australia (Reg key: 448334). This work was supported by Cancer Research UK, the EU IP6 Consortium on DNA Repair, the Breast Cancer Campaign, the Louis-Jeantet Foundation, and the Fanconi Anemia Research Fund.