The Fanconi Anemia DNA Repair Pathway: Structural and Functional Insights into a Complex Disorder

Abstract

Mutations in any of at least sixteen FANC genes (FANCA-Q) cause Fanconi anemia, a disorder characterized by sensitivity to DNA interstrand crosslinking agents. The clinical features of cytopenia, developmental defects, and tumor predisposition are similar in each group, suggesting that the gene products participate in a common pathway. The Fanconi anemia DNA repair pathway consists of an anchor complex that recognizes damage caused by interstrand crosslinks, a multisubunit ubiquitin ligase that monoubiquitinates two substrates, and several downstream repair proteins including nucleases and homologous recombination enzymes. We review progress in the use of structural and biochemical approaches to understanding how each FANC protein functions in this pathway.

Fanconi anemia: a model disease for studies on human genetics and advanced therapeutics

“…The ID complex promotes nucleolytic cleavage of the 3´ and 5´ sites of DNA to unhook the ICL and successively induces trans-lesion polymerases Rev1 and pol [39][40][41][42]. These reactions extend the leading DNA strand above and past the unhooked ICL to produce a substrate that is processed by successive HRR reactions [34].…”

Genetic controls of DNA damage avoidance in response to acetaldehyde in fission yeast

“…Both DPCs and ICLs have a propensity to disrupt the DNA replication process, causing DNA damage and genomic instability, hallmarks of cancers. 6 The Fanconi anemia (FA) pathway plays a critical role in the repair of ICLs, [7][8][9][10] although the role of this pathway in DPC repair has not yet been well understood. 11 Fanconi anemia is an inherited disease that is characterized by bone marrow failure and a strong predisposition to cancer.…”

Fanconi Anaemia: A Case Report in Nigeria

“…FA is a rare genetic disease due to defect in a cluster of protein required for DAN repair (12) . It is therefore necessary to look out for anaemia, immune problems, digestive disorders and leukaemia in the family history (4,14) . The visible symptoms in FA individuals may present at birth or may start manifesting between the ages of 2 and 15 years (4) .…”