Fanconi anemia and the cell cycle: new perspectives on aneuploidy.
Fanconi anemia (FA) is a complex heterogenic disorder of genomic instability, bone marrow failure, cancer predisposition, and congenital malformations. The FA signaling network orchestrates the DNA damage recognition and repair in interphase as well as proper execution of mitosis. Loss of FA signaling causes chromosome instability by weakening the spindle assembly checkpoint, disrupting centrosome maintenance, disturbing resolution of ultrafine anaphase bridges, and dysregulating cytokinesis. Thus, the FA genes function as guardians of genome stability throughout the cell cycle. This review discusses recent advances in diagnosis and clinical management of Fanconi anemia and presents the new insights into the origins of genomic instability in FA. These new discoveries may facilitate the development of rational therapeutic strategies for FA and for FA-deficient malignancies in the general population.
Department of Pediatrics, Indiana University School of Medicine, Riley Hospital for Children 705 Riley Hospital Drive, Indianapolis, IN 46202 USA ; Division of Pediatric Hematology-Oncology, Indiana University School of Medicine, Riley Hospital for Children 705 Riley Hospital Drive, Indianapolis, IN 46202 USA ; Department of Medical and Molecular Genetics, Wells Center for Pediatric Research 1044 W. Walnut Street, Indiana University School of Medicine, Indianapolis, IN 46202 USA.
Grzegorz
G
Nalepa
Department of Pediatrics, Indiana University School of Medicine, Riley Hospital for Children 705 Riley Hospital Drive, Indianapolis, IN 46202 USA ; Department of Medical and Molecular Genetics, Wells Center for Pediatric Research 1044 W. Walnut Street, Indiana University School of Medicine, Indianapolis, IN 46202 USA ; Department of Microbiology and Immunology, Wells Center for Pediatric Research 1044 W. Walnut Street, Indiana University School of Medicine, Indianapolis, IN 46202 USA ; Department of Biochemistry and Molecular Biology, Wells Center for Pediatric Research 1044 W. Walnut Street, Indiana University School of Medicine, Indianapolis, IN 46202 USA.
D Wade
DW
Clapp