FANC proteins

FANC Proteins

FANC proteins are a group of proteins associated with Fanconi anemia, a rare genetic disorder that affects the bone marrow and results in decreased production of all types of blood cells. These proteins are crucial for the repair of DNA damage, particularly interstrand crosslinks, which can lead to chromosomal instability if not properly repaired.

Overview

Fanconi anemia (FA) is a genetically heterogeneous disorder, meaning it can be caused by mutations in any one of several different genes. The proteins encoded by these genes are collectively known as FANC proteins. To date, at least 22 different FANC genes have been identified, each designated by a letter (e.g., FANCA, FANCB, FANCC, etc.).

Function

FANC proteins play a critical role in the DNA repair pathway known as the Fanconi anemia pathway. This pathway is responsible for repairing DNA interstrand crosslinks, which are lesions that covalently link the two strands of the DNA double helix, preventing their separation and thus blocking replication and transcription.

The core complex of FANC proteins, which includes FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL, and FANCM, is responsible for monoubiquitinating the FANCD2 and FANCI proteins. This modification is crucial for the recruitment of downstream repair factors to the site of damage.

Clinical Significance

Mutations in FANC genes lead to Fanconi anemia, characterized by bone marrow failure, congenital abnormalities, and an increased risk of cancer, particularly acute myeloid leukemia and squamous cell carcinomas. Patients with FA often present with physical abnormalities such as short stature, skin pigmentation changes, and skeletal malformations.

Research and Therapeutic Approaches

Research into FANC proteins has provided significant insights into the mechanisms of DNA repair and the maintenance of genomic stability. Understanding these processes is crucial for developing therapies for FA and other diseases associated with DNA repair defects.

Gene therapy, hematopoietic stem cell transplantation, and the use of androgens and hematopoietic growth factors are some of the therapeutic approaches being explored to treat FA. Additionally, small molecule inhibitors that target specific components of the FA pathway are under investigation as potential treatments for cancers with defects in DNA repair.

See Also

• Fanconi anemia
• DNA repair
• Genomic instability

References

• D'Andrea, A. D. (2010). "Susceptibility pathways in Fanconi's anemia and breast cancer." *The New England Journal of Medicine*, 362(20), 1909-1919.
• Kottemann, M. C., & Smogorzewska, A. (2013). "Fanconi anaemia and the repair of Watson and Crick DNA crosslinks." *Nature*, 493(7432), 356-363.