Abstract
DNA interstrand crosslink repair requires several classes of proteins, including structure-specific endonucleases and Fanconi anemia proteins. SLX4, which coordinates three separate endonucleases, was recently recognized as an important regulator of DNA repair. Here we report the first human individuals found to have biallelic mutations in SLX4. These individuals, who were previously diagnosed as having Fanconi anemia, add SLX4 as an essential component to the FA-BRCA genome maintenance pathway.
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Acknowledgements
We thank the affected individuals and their families for contributing to this study. We also thank A. Raams, R. Friedl, B. Gottwald and S. Darchinger for expert technical assistance. We acknowledge I. Carr for Phaser software, R. Kanaar for RAD51 antiserum and K.J. Patel for mouse Slx4 cDNA. Financial support was from the Cancer Center Amsterdam-VU Medisch Centrum Institute for Cancer and Immunology (CCA/V-ICI) Amsterdam (to C.S.), the Dutch Cancer Society (to H.J.), Schroeder-Kurth-Fund (to D.S.) and the Medical Research Council UK (to J.R.).
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The study was designed by J.P.d.W., J.R., D.S. and H.J. Clinical information of affected individuals and referral for Fanconi anemia diagnosis was coordinated by E.T.K. and Y.H.-H. Fanconi anemia diagnosis was confirmed by A.W.M.N. SNP array studies were coordinated by T.B. Mutational analysis and functional studies were carried out by C.S., K.H., B.S., M.A.R., J.S., A.B.O. and K.E. The ERCC1 focus formation assay was coordinated by N.G.J.J. The manuscript was written by C.S., J.P.d.W., J.R. and D.S., with help from the other authors.
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Stoepker, C., Hain, K., Schuster, B. et al. SLX4, a coordinator of structure-specific endonucleases, is mutated in a new Fanconi anemia subtype. Nat Genet 43, 138–141 (2011). https://doi.org/10.1038/ng.751
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DOI: https://doi.org/10.1038/ng.751
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