Çocuk Sağlığı ve Hastalıkları Dergisi 2003 , Vol 46 , Num 4
Genetic and molecular basis of Fanconi anemia: an interesting model of a multigenic disorder interacting with breast cancer (BRCA1, BRCA2) and ataxia telangiectasia (ATM) pathways
Günay Balta1, Fatma Gümrük2, Çiğdem Altay3
Hacettepe Üniversitesi Çocuk Sağlığı Enstitüsü 1Moleküler Genetik Doktoru, Tıp Fakültesi, 2Pediatri Profesörü, 3Emekli Pediatri Profesörü Fanconi anemia (FA) is an autosomal recessive disorder characterized by multiple congenital abnormalities, bone marrow failure, cancer susceptibility and cellular sensitivity to cross-linking agents. To date, at least eight complementation groups (A-C, D1, D2, E-G) have been described and seven FA genes have been cloned. The protein products of these genes interact in a common pathway in response to DNA damage with cross-linking agents or during the S-phase of cell cycle. Five FA proteins (A, C, E, F, G) form a nuclear complex and mediate activation of D2 protein (FANCD2) by monoubiquitination. Activated FANCD2 is targeted to a nuclear DNA repair foci where it interacts with the breast cancer susceptibility (BRCA1, BRCA2) and other DNA repair proteins. Recent studies have revealed that FANCD1 and BRCA2 are in fact the same gene. On the other hand, the ataxia telangiectasia kinase (ATM) phosphorylates FANCD2 protein in response to ionizing radiation. Phosphorylated FANCD2 activates S-phase checkpoint to arrest cell cycle progression and allow time for DNA repair. These findings have indicated that FANCD2 functions at the intersection of two independent signaling pathways of the DNA repair. Anahtar Kelimeler : Fankoni anemisi, genetik, moleküler temeller, meme kanseri, ataksi telenjektazi, Fanconi anemia, genetics, molecular basis, breast cancer, ataxia telangiectasia
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