Review
Version 2
Preserved in Portico This version is not peer-reviewed
Chromosome Instability in Fanconi Anemia: From Breaks to Phenotypic Consequences
Version 1
: Received: 19 November 2020 / Approved: 23 November 2020 / Online: 23 November 2020 (08:51:42 CET)
Version 2 : Received: 21 December 2020 / Approved: 22 December 2020 / Online: 22 December 2020 (10:58:20 CET)
Version 2 : Received: 21 December 2020 / Approved: 22 December 2020 / Online: 22 December 2020 (10:58:20 CET)
A peer-reviewed article of this Preprint also exists.
García-de-Teresa, B.; Rodríguez, A.; Frias, S. Chromosome Instability in Fanconi Anemia: From Breaks to Phenotypic Consequences. Genes 2020, 11, 1528. García-de-Teresa, B.; Rodríguez, A.; Frias, S. Chromosome Instability in Fanconi Anemia: From Breaks to Phenotypic Consequences. Genes 2020, 11, 1528.
Abstract
Abstract: Fanconi anemia (FA), a chromosomal instability syndrome, is caused by inherited pathogenic variants in any of 22 FANC genes, that cooperate in the FA/BRCA pathway. This pathway regulates the repair of DNA interstrand crosslinks (ICLs) through homologous recombination. In FA proper repair of ICLs is impaired, and accumulation of toxic DNA double strand breaks occurs. In order to repair this type of DNA damage, FA cells activate alternative error-prone DNA repair pathways, that may lead to the formation of gross structural chromosome aberrations of which radial figures are the hallmark of FA and their segregation during cell division are the origin of subsequent aberrations like translocations, dicentrics and acentric fragments. The deficiency in DNA repair has pleiotropic consequences in the phenotype of patients with FA, including developmental alterations, bone marrow failure and an extreme risk to develop cancer. The mechanisms leading to the physical abnormalities during embryonic development have not been clearly elucidated, however FA has features of premature aging with chronic inflammation mediated by pro-inflammatory cytokines, that results in tissue attrition, selection of malignant clones and cancer onset. Moreover, the effect of the FA/BRCA pathway in germinal cells, evidenced by infertility in patients with FA attests of chromosomal instability and cell death also occurring in the germinal compartment.
Keywords
Chromosomal instability; FA pathway; Radial figures; TGF pathway; MYC; p53; Bone marrow failure; cancer; physical abnormalities; infertility.
Subject
Medicine and Pharmacology, Immunology and Allergy
Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Comments (1)
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Commenter: Sara Frias
Commenter's Conflict of Interests: Author
A new section was added: Fanconi anemia proteins beyond ICL repair
And in general, figures and text were improved.