Faap20, also known as 20-kDa FANCA-associated protein, is a key component of the Fanconi anemia (FA) core complex. It plays essential roles in DNA repair pathways, particularly in homology-directed repair of DNA double-strand breaks. It promotes FANCD2/FANCI monoubiquitination and activates the damage response to interstrand crosslink damage, which is crucial for maintaining genome integrity [1,2,3].

Deletion of Faap20 in mice led to a mild FA-like phenotype, with defects in the reproductive and hematopoietic systems. Faap20 -/- mice were susceptible to mitomycin C-induced pancytopenia, and their hematopoietic stem and progenitor cells (HSPCs) showed defects in long-term multilineage reconstitution. Faap20 -/- HSPCs also displayed an aberrant cell cycle pattern during chronic MMC treatment. Using Faap20 -/- Fanca -/- double-knockout mice, a possible dominant effect of FANCA in the interaction between FAAP20 and FANCA was demonstrated [4].

In conclusion, Faap20 is vital for DNA repair and genome maintenance, especially in the context of the FA pathway. The Faap20 knockout mouse model has provided valuable insights into the role of Faap20 in hematopoietic function and the progression of bone marrow failure-related diseases similar to those seen in FA patients [4].

References:

1. Palovcak, Anna, Yuan, Fenghua, Verdun, Ramiro, Luo, Liang, Zhang, Yanbin. 2023. Fanconi anemia associated protein 20 (FAAP20) plays an essential role in homology-directed repair of DNA double-strand breaks. In Communications biology, 6, 873. doi:10.1038/s42003-023-05252-9. https://pubmed.ncbi.nlm.nih.gov/37620397/

2. Wang, Jingming, Chan, Bryan, Tong, Michael, Haley, John, Kim, Hyungjin. 2019. Prolyl isomerization of FAAP20 catalyzed by PIN1 regulates the Fanconi anemia pathway. In PLoS genetics, 15, e1007983. doi:10.1371/journal.pgen.1007983. https://pubmed.ncbi.nlm.nih.gov/30789902/

3. Ali, Abdullah Mahmood, Pradhan, Arun, Singh, Thiyam Ramsingh, Pang, Qishen, Meetei, Amom Ruhikanta. 2012. FAAP20: a novel ubiquitin-binding FA nuclear core-complex protein required for functional integrity of the FA-BRCA DNA repair pathway. In Blood, 119, 3285-94. doi:10.1182/blood-2011-10-385963. https://pubmed.ncbi.nlm.nih.gov/22343915/

4. Zhang, Tingting, Wilson, Andrew F, Mahmood Ali, Abdullah, Ruhikanta Meetei, Amom, Pang, Qishen. 2015. Loss of Faap20 Causes Hematopoietic Stem and Progenitor Cell Depletion in Mice Under Genotoxic Stress. In Stem cells (Dayton, Ohio), 33, 2320-30. doi:10.1002/stem.2048. https://pubmed.ncbi.nlm.nih.gov/25917546/