Chapter Category: DNA

From the book DNA Repair and Human Disease

The Fanconi Anemia/BRCA Pathway: FANCD2 at the Crossroad between Repair and Checkpoint Responses to DNA Damage

Massimo Bogliolo and Jordi Surralles

Studies on cancer-prone and rare human genetic disorders often lead to significant advances in our understanding of the complex network of genome stability and DNA repair pathways that have evolved in the human genome to prevent the harmful effects of exposure to DNA damaging agents. One such disorder is Fanconi Anemia, an autosomal recessive disease characterized by an increased spontaneous and DNA cross-linkers induced chromosome instability, progressive pancytopenia and cancer susceptibility. At least eleven genes are involved in Fanconi anemia, including the breast cancer susceptibility gene BRCA2. Six of the Fanconi anemia proteins (FANCA, C, E, F, G and L) assemble in a complex that is required for FANCD2 activation by monoubiquitination in response to DNA damage or during S-phase progression. Active FANCD2 then colocalizes with the product of the breast cancer susceptibility gene BRCA1 in discrete nuclear foci. FANCD2 is also independently phosphorylated by ATM in response to ionising radiation and interacts with the MRE11/Rad50/NBS1 complex, which is directly involved in homologous recombination DNA repair pathway and in cell cycle checkpoint response to DNA damage. Available data indicate that FANCD2 is involved in cell cycle regulation and DNA repair. Our current knowledge on the functional significance of FA pathway and more specifically FANCD2 and its interacting proteins in pathways of genomic surveillance and maintenance will be discussed in this chapter.

Taken from the book

DNA Repair and Human Disease

Edited by: Adayabalam Balajee

More chapters from the book:

RecQ family DNA helicases are defined by amino acid sequence similarities to Escherichia coli RecQ which has been known to act in homologous recombination and tosuppress illegitimate recombination, particularly during the repair of DNA doublestrand breaks. Five RecQ family genes have been...


Down’s syndrome (DS) is an autosomal recessive human disorder caused by an extracopy of chromosome 21. DS patients are characterized by dwarfism and mental retardation accompanied by an increased incidence of cancer development in varioustissues and organs. DS patients also show signs of...


Studies on cancer-prone and rare human genetic disorders often lead to significantadvances in our understanding of the complex network of genome stability and DNArepair pathways that have evolved in the human genome to prevent the harmful effectsof exposure to DNA damaging agents. One such...


Xeroderma pigmentosum (XP),1 Cockayne syndrome (CS)2,3 and xerodermapigmentosum-Cockayne syndrome (XP-CS)4,5 are rare disorders with autosomal recessiveinheritance, characterized by extreme sensitivity to sunlight. This sensitivity reflectsthe inadequate removal and/or repair of UV-induced...


Ataxia telangiectasia (AT) is an autosomal recessive multisystem human disorder andpatients are characterized by cerebellar ataxia, oculocutaneous telangiectasia, immunodeficiency, chromosomal instability and radio sensitivity with an increased predispositionto lymphoid cancer in childhood....


Loss of telomere homeostasis via chromosome-genomic instability might effectively promote tumour progression. Telomere function may have contrasting roles: inducing replicative senescence and promoting tumourigenesis and these roles may vary between celltypes depending on the expression of...


Roles of the BRCA1 and BRCA2 Breast Cancer Susceptibility Proteins in DNA Repair
Katrin Gudmundsdottir, Emily Witt and Alan Ashworth

Since the cloning of the BRCA1 and BRCA2 genes less than 10 years ago, a great deal ofeffort has been expended in attempting to uncover the functions of the encoded proteins.BRCA1 and BRCA2 have now been linked to a wide variety of cellular functionsthrough binding or colocalization with...


Werner’s syndrome (WS) and Cockayne syndrome (CS) are rare human autosomalrecessive disorders classified as segmental progeroid disorders. WS is marked bypremature onset of age-related phenotypic changes (such as cataract and greying ofhair etc) and genome instability. Cells derived from...


Trichothiodystrophy (TTD) is a rare autosomal recessive multisystem disorder characterizedby sulfur-deficient brittle hair, mental and physical retardation, ichthyosis, and,in many patients, cutaneous photosensitivity but no cancer incidence. All sun-sensitiveTTD cases appear to be...


Mechanisms of DNA Damage and Repair in Alzheimer Disease
V. Prakash Reddy, George Perry, Marcus S. Cooke, Lawrence M. Sayre and Mark A. Smith

Reactive oxygen species (ROS) are produced during the respiratory cycle in mitochon- dria,1 as well as normal cellular and xenobiotic metabolism. Exposure to various noxious insults can also lead to ROS production. In addition, ROS are also generated through metal-catalyzed reactions. A...


Advertisements