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FANCD2

FANCD2. and its role in FA and other Cancers. Christina Miller. Fanconi Anemia is a congenital cancer predisposition syndrome that causes chromosomal instability. Bone marrow failure Sensitivity to cross-linking agents. FANCD2 is expressed in tissues where proliferation occurs.

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FANCD2

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  1. FANCD2 and its role in FA and other Cancers Christina Miller

  2. Fanconi Anemia is a congenital cancer predisposition syndrome that causes chromosomal instability • Bone marrow failure • Sensitivity to cross-linking agents

  3. FANCD2 is expressed in tissues where proliferation occurs http://dx.doi.org.libproxy.lib.unc.edu/10.1016/S1097-2765(01)00172-1

  4. FANCD2 is regulated by post Translational Modification • Monoubiquitinated on Lys-561 • Necessary for binding to chromatin • Phosphorylated by ATM or ATR on Ser-222 http://dx.doi.org/10.1016/j.mrfmmm.2005.05.010 http://www.scills.ac.uk/arno-alpi-research.shtml

  5. Interstrand Cross-links are covalent bonds that link DNA strands and block replication Frontiers in Bioscience 9, 421-437, January 1, 2004

  6. FANCD2 is necessary for replication-dependent ICL repair https://walter.hms.harvard.edu/node/11 Nature Reviews Cancer3, 23-34 (January 2003)

  7. FANCD2 is also active in S Phase arrest pathway Nature Reviews Cancer 3, 23-34 (January 2003) http://dx.doi.org/10.1016/j.dnarep.2004.04.005

  8. FANCD2-/- mice show phenotypes similar to those of FA patients • FANCD2-/- mutant eye one day after birth • Wild type and FANCD2-/- mutant one day after birth • Wild type eye one day after birth Genes Dev. 2003 August 15; 17(16): 2021–2035.

  9. Reduced FANCD2 expression is correlated with decreased survival of breast cancer patients Am J Pathol. 2010 June; 176(6): 2935–2947.

  10. References • Dronkert MLG, Kanaar R. Repair of DNA interstrand cross-links. Mutat Res /DNA Repair. 2001 9/4;486(4):217-47. • Grompe M, D'Andrea A. Fanconi anemia and DNA repair. Hum Mol Genet. 2001;10:2253. • HölzelM, van Diest PJ, Bier P, Wallisch M, Hoatlin ME, Joenje H, et al. FANCD2 protein is expressed in proliferating cells of human tissues that are cancer‐prone in fanconianaemia. The Journal of Pathology. 2003;201(2):198-203. • Houghtaling S, Timmers C, Noll M, Finegold MJ, Jones SN, Meyn MS, et al. Epithelial cancer in fanconi anemia complementation group D2 (Fancd2) knockout mice. Genes & development. 2003;17(16):2021-35. • Rudland PS, Platt-Higgins AM, Davies LM, et al. Significance of the Fanconi anemia FANCD2 protein in sporadic and metastatic human breast cancer. American Journal of Pathology.2010;176(6):2935–2947. • Shukla P, Ghosh K, Vundinti BR. Current and emerging therapeutic strategies for fanconi anemia. The HUGO Journal. 2012;6(1):1-8. • Venkitaraman AR. Tracing the network connecting BRCA and fanconianaemia proteins. Nature reviews. Cancer. 2004;4(4):266-76. • Wang X, D’Andrea AD. The interplay of fanconi anemia proteins in the DNA damage response. DNA Repair. 2004 0;3(8–9):1063-9.

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