FANCG

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FANCG is a human gene that makes a protein involved in repairing DNA damage. It is part of the Fanconi anemia (FA) repair pathway and defines complementation group G. Mutations in FANCG can cause Fanconi anemia, a recessive disorder that often includes bone marrow failure, birth defects, and an increased risk of cancer. The FANCG protein is about 622 amino acids long and has an N-terminal leucine-zipper motif.

In cells, FANCG is part of a nuclear multiprotein complex with other FA proteins (FANCA, FANCB, FANCC, FANCE, FANCF, FANCL, FANCM). This complex is required to activate FANCD2 by mono-ubiquitination after DNA damage, a key step in repairing DNA interstrand crosslinks. Activated FANCD2 co-localizes with BRCA1 at damage sites and may help prepare chromosomes for recombination during meiosis.

FANCG interacts with BRCA2 and other FA proteins, forming a coordinated repair pathway. In mice, FANCG is expressed in reproductive cells and neural tissue; mice lacking FANCG show fertility problems in both sexes and neural progenitor cell death during forebrain development, which can lead to long-term depletion of the neural stem cell pool.

Overall, Fanconi anemia arises from failures to repair DNA damage, especially crosslinks, leading to bone marrow failure, developmental defects, cancer risk, and features that resemble premature aging of stem cells. FANCG helps the cell sense damage and coordinate repair through the FANCD2 pathway and its interactions with BRCA proteins.