Download - FANCD2
FANCD2and 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
http://dx.doi.org.libproxy.lib.unc.edu/10.1016/S1097-2765(01)00172-1
FANCD2 is regulated by post Translational Modification
Monoubiquitinated on Lys-561o Necessary for binding to
chromatin
Phosphorylated by ATM or ATR on Ser-222
http://www.scills.ac.uk/arno-alpi-research.shtml
http://dx.doi.org/10.1016/j.mrfmmm.2005.05.010
Interstrand Cross-links are covalent bonds that link DNA strands and block
replication
Frontiers in Bioscience 9, 421-437, January 1, 2004
FANCD2 is necessary for replication-dependent
ICL repair
https://walter.hms.harvard.edu/node/11
Nature Reviews Cancer 3, 23-34 (January 2003)
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
FANCD2-/- mice show phenotypes similar to those
of FA patients
FANCD2-/- mutant eye one day after birth
Wild type eye one day after birth
Wild type and FANCD2-/- mutant one day after birth
Genes Dev. 2003 August 15; 17(16): 2021–2035.
Reduced FANCD2 expression is correlated with decreased survival of breast
cancer patients
Am J Pathol. 2010 June; 176(6): 2935–2947.
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. Hölzel M, 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 fanconi anaemia. 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 fanconi anaemia 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.