Faap20, also known as 20-kDa FANCA-associated protein, is an integral component of the Fanconi anemia (FA) core complex. It plays a crucial role in the FA-BRCA DNA repair pathway, which is essential for maintaining genome integrity in response to DNA interstrand cross-links (ICLs) and other DNA damage [2]. Faap20 is involved in promoting FANCD2/FANCI monoubiquitination, a key step in activating the damage response to ICLs. Additionally, it participates in homology-directed repair of DNA double-strand breaks [1].

Deletion of Faap20 in mice led to a mild FA-like phenotype with defects in the reproductive and hematopoietic systems [3]. Hematopoietic stem and progenitor cells (HSPCs) from Faap20 -/- mice showed defects in long-term multilineage reconstitution in lethally irradiated recipient mice. Faap20 -/- mice are also susceptible to mitomycin C (MMC)-induced pancytopenia, with acute MMC stress causing significant progenitor loss, especially in erythroid progenitors and megakaryocyte-erythrocyte progenitors. During chronic MMC treatment, Faap20 -/- HSPCs displayed an aberrant cell cycle pattern [3].

In conclusion, Faap20 is essential for DNA repair, especially in the context of the FA-BRCA pathway. The Faap20 knockout mouse model has been valuable in revealing its role in hematopoietic function and the response to genotoxic stress, providing insights into the pathogenesis of FA-related bone marrow failure and other associated diseases [3].