%0 Journal Article
%T Current and emerging therapeutic strategies for Fanconi anemia
%A Pallavi Shukla
%A Kanjaksha Ghosh
%A Babu R Vundinti
%J The HUGO Journal
%D 2012
%I BioMed Central
%R 10.1186/1877-6566-6-1
%X Fanconi anemia (FA) is an autosomal recessive disorder (OMIM 227650). It is characterized by bone marrow failure (aplastic anemia), developmental delay, physical abnormalities such as short stature; microcephaly; abnormal skin pigmentation; malformations of skeletal system, limbs, eyes, ears, kidneys and urinary tract, heart, genitalia, gastrointestinal system and central nervous system; and increased incidence of solid tumors and leukemias (Auerbach et al. 2001; D'Andrea and Grompe 1997). To date, around 14 genes are responsible for known complementation FA groups: A, B, C, D1 [BRCA2], D2, E, F, G, I, J [BRIP1], L, M, N [PALB2] and P [SLX4] are known. There are three other genes RAD51C, DDX11, FAAP20 which are involved in the pathway, but not formally designated as FA genes (Svahn and Dufour 2011). FA proteins play an important role in repair of DNA damage. When DNA damage occurs, the FA proteins, A, B, C, E, F, G, I, L, and M at upstream of the pathway monoubiquitinate FANCD2 protein, resulting in targeting of protein in nuclear foci. FANCD2 then interacts with BRCA1 and other DNA damage response proteins downstream of the FA pathway such as BRCA2, RAD51 and NBS to repair the damage (Wang et al. 2004) (Figure 1). Alterations in FA-pathway proteins has also been reported in various types of cancers such as breast cancer, ovarian cancer, lung cancer, cervical cancer, pancreatic cancer etc (Dhillon et al. 2004; Marsit et al. 2004, Narayan et al. 2004; Taniguchi et al. 2003; van Der Heijden et al. 2003). Thus, FA proteins take part in DNA damage repair directly or indirectly. Indirect role of FA proteins in repairing the DNA damage is by triggering a cell cycle checkpoint (Sala-Trepat et al. 2000).FA proteins are also known to interact with other proteins such as FANCA and FANCC with ¦Á spectrin II; FANCC with cytochrome P-450 reductase and with glutathione S-transferase, Hsp70, STAT1; and FANCG with cytochrome P-450 2E1 (McMahon et al. 1999; Pagano and Youssoufian, 20
%K Fanconi Anemia
%K Androgens
%K Haematopoitic growth factors
%K Haematopoietic stem cell transplantation
%K Gene therapy
%K Small molecule intervention
%K DNA repair pathway
%U http://www.thehugojournal.com/content/6/1/1