Abstract
Fanconi anemia (FA) is a rare genetic disorder characterized by bone marrow failure, developmental abnormalities and a predisposition to cancer, particularly acute myeloid leukemia. So far, 22 FA genes (FANCA-W) have been identified. Germline inactivation of any one of the 22 currently known FA genes causes FA. Proteins encoded by FA genes are involved in the Fanconi anemia pathway, which repairs DNA interstrand crosslinks (ICLs). The main function of the FA pathway in repairing ICLs has been extensively studied. In addition, several lines of evidence indicate that the FA pathway has crucial roles in genome maintenance upon replication stress, and is involved in common fragile sites, R-loops, and mitotic DNA synthesis. Recently, we found that all the functions of the FA pathway are possibly derived from one unified mechanism, namely that FA proteins play a role in the cleavage-coupled break-induced replication pathway to restart stalled replication forks. In the review, we summarize our current understanding of the functions of the FA pathway, and review our knowledge of the potential endogenous pathogenic factors that contribute to FA.
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Acknowledgements
This work was supported in part by the National Natural Science Foundation of China (32071285 and 31870807) to R.G.
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Xu, X., Guo, R. & Xu, D. The emergence of a unified mechanism in the Fanconi anemia pathway. GENOME INSTAB. DIS. 2, 281–291 (2021). https://doi.org/10.1007/s42764-021-00053-y
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DOI: https://doi.org/10.1007/s42764-021-00053-y