FANCD2: DNA Repair and Beyond

Mon, 10/14/2013 - 13:20

Fanconi anemia (FANC) is a heterogenous, autosomal-recessive cancer susceptibility genetic disorder that is characterized by a wide array of symptoms, including congenital defects, progressive bone marrow failure due to DNA-damage hypersensitivity, chromosomal instability, and poor DNA repair. The protein FANCD2 is involved in mediating cellular resistance to DNA cross-linking and DNA synthesis arrest that is triggered by ionizing radiation (IR). The FANCD2 antibody was used to further characterize how oxidative stress and damage trigger formation of a multimeric nuclear complex of various FANC gene products, which in turn activates FANCD2 through FANCD2 monoubiquitination (1).  Danish researchers employed the FANCD2 antibody in provocative chromatin spatial colocalization studies (2). Based on their data, they propose that the surveillance of genome regulators (ie repair factors such as Rad genes and BRCA1) and their accumulation within subchromatin microcompartments - as monitored by the FANCD2 antibody - is a useful tool in the classification of cellular responses to DNA double-stranded breaks (DSB) (2).

Immunohistochemistry: FANCD2 Antibody Immunohistochemistry: FANCD2 Antibody

Further DSB studies with FANCD2 antibody focusing on the RNF8 ubiquitin ligase pathway demonstrated that ATM protein kinase phosphorylates the DNA-damage mediator protein MDC1 to recruit genome regulator factors to DNA damage sites, as well as to enable resistance to ionizing radiation (3). Characterization studies on DNA damage response pathway defects and disruptions in breast cancer used the FANCD2 antibody to help establish and validate a novel ex vivo foci biomarker assay in tumor biopsies capable of detecting the presence of both pre-existing and functionally important defects (4).

  1. PMID: 15138265
  2. PMID: 16618811
  3. PMID: 18006705
  4. PMID: 19671671

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