Canonical and Noncanonical Roles of Fanconi Anemia Proteins: Implications in Cancer Predisposition
Fanconi anemia (FA) is a clinically and genetically heterogeneous disorder characterized by the variable presence of congenital somatic abnormalities, bone marrow failure (BMF), and a predisposition to develop cancer. Monoallelic germline mutations in at least five genes involved in the FA pathway a...
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| Format: | Article |
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MDPI AG
2020-09-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/12/9/2684 |
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| author | Giacomo Milletti Luisa Strocchio Daria Pagliara Katia Girardi Roberto Carta Angela Mastronuzzi Franco Locatelli Francesca Nazio |
| author_facet | Giacomo Milletti Luisa Strocchio Daria Pagliara Katia Girardi Roberto Carta Angela Mastronuzzi Franco Locatelli Francesca Nazio |
| author_sort | Giacomo Milletti |
| collection | DOAJ |
| description | Fanconi anemia (FA) is a clinically and genetically heterogeneous disorder characterized by the variable presence of congenital somatic abnormalities, bone marrow failure (BMF), and a predisposition to develop cancer. Monoallelic germline mutations in at least five genes involved in the FA pathway are associated with the development of sporadic hematological and solid malignancies. The key function of the FA pathway is to orchestrate proteins involved in the repair of interstrand cross-links (ICLs), to prevent genomic instability and replication stress. Recently, many studies have highlighted the importance of FA genes in noncanonical pathways, such as mitochondria homeostasis, inflammation, and virophagy, which act, in some cases, independently of DNA repair processes. Thus, primary defects in DNA repair mechanisms of FA patients are typically exacerbated by an impairment of other cytoprotective pathways that contribute to the multifaceted clinical phenotype of this disease. In this review, we summarize recent advances in the understanding of the pathogenesis of FA, with a focus on the cytosolic noncanonical roles of FA genes, discussing how they may contribute to cancer development, thus suggesting opportunities to envisage novel therapeutic approaches. |
| first_indexed | 2024-03-10T16:11:28Z |
| format | Article |
| id | doaj.art-33c0cef97771442b8f8c0d7621d47443 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T16:11:28Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-33c0cef97771442b8f8c0d7621d474432023-11-20T14:24:21ZengMDPI AGCancers2072-66942020-09-01129268410.3390/cancers12092684Canonical and Noncanonical Roles of Fanconi Anemia Proteins: Implications in Cancer PredispositionGiacomo Milletti0Luisa Strocchio1Daria Pagliara2Katia Girardi3Roberto Carta4Angela Mastronuzzi5Franco Locatelli6Francesca Nazio7Department of Pediatric Hemato-Oncology and Cell and Gene Therapy, Istituto di Ricovero e Cura a Carattere Scientifico Bambino Gesù Children’s Hospital, 00146 Rome, ItalyDepartment of Pediatric Hemato-Oncology and Cell and Gene Therapy, Istituto di Ricovero e Cura a Carattere Scientifico Bambino Gesù Children’s Hospital, 00146 Rome, ItalyDepartment of Pediatric Hemato-Oncology and Cell and Gene Therapy, Istituto di Ricovero e Cura a Carattere Scientifico Bambino Gesù Children’s Hospital, 00146 Rome, ItalyDepartment of Pediatric Hemato-Oncology and Cell and Gene Therapy, Istituto di Ricovero e Cura a Carattere Scientifico Bambino Gesù Children’s Hospital, 00146 Rome, ItalyDepartment of Pediatric Hemato-Oncology and Cell and Gene Therapy, Istituto di Ricovero e Cura a Carattere Scientifico Bambino Gesù Children’s Hospital, 00146 Rome, ItalyDepartment of Pediatric Hemato-Oncology and Cell and Gene Therapy, Istituto di Ricovero e Cura a Carattere Scientifico Bambino Gesù Children’s Hospital, 00146 Rome, ItalyDepartment of Pediatric Hemato-Oncology and Cell and Gene Therapy, Istituto di Ricovero e Cura a Carattere Scientifico Bambino Gesù Children’s Hospital, 00146 Rome, ItalyDepartment of Pediatric Hemato-Oncology and Cell and Gene Therapy, Istituto di Ricovero e Cura a Carattere Scientifico Bambino Gesù Children’s Hospital, 00146 Rome, ItalyFanconi anemia (FA) is a clinically and genetically heterogeneous disorder characterized by the variable presence of congenital somatic abnormalities, bone marrow failure (BMF), and a predisposition to develop cancer. Monoallelic germline mutations in at least five genes involved in the FA pathway are associated with the development of sporadic hematological and solid malignancies. The key function of the FA pathway is to orchestrate proteins involved in the repair of interstrand cross-links (ICLs), to prevent genomic instability and replication stress. Recently, many studies have highlighted the importance of FA genes in noncanonical pathways, such as mitochondria homeostasis, inflammation, and virophagy, which act, in some cases, independently of DNA repair processes. Thus, primary defects in DNA repair mechanisms of FA patients are typically exacerbated by an impairment of other cytoprotective pathways that contribute to the multifaceted clinical phenotype of this disease. In this review, we summarize recent advances in the understanding of the pathogenesis of FA, with a focus on the cytosolic noncanonical roles of FA genes, discussing how they may contribute to cancer development, thus suggesting opportunities to envisage novel therapeutic approaches.https://www.mdpi.com/2072-6694/12/9/2684Fanconi anemiaDNA repairmitochondriacancersinflammation |
| spellingShingle | Giacomo Milletti Luisa Strocchio Daria Pagliara Katia Girardi Roberto Carta Angela Mastronuzzi Franco Locatelli Francesca Nazio Canonical and Noncanonical Roles of Fanconi Anemia Proteins: Implications in Cancer Predisposition Cancers Fanconi anemia DNA repair mitochondria cancers inflammation |
| title | Canonical and Noncanonical Roles of Fanconi Anemia Proteins: Implications in Cancer Predisposition |
| title_full | Canonical and Noncanonical Roles of Fanconi Anemia Proteins: Implications in Cancer Predisposition |
| title_fullStr | Canonical and Noncanonical Roles of Fanconi Anemia Proteins: Implications in Cancer Predisposition |
| title_full_unstemmed | Canonical and Noncanonical Roles of Fanconi Anemia Proteins: Implications in Cancer Predisposition |
| title_short | Canonical and Noncanonical Roles of Fanconi Anemia Proteins: Implications in Cancer Predisposition |
| title_sort | canonical and noncanonical roles of fanconi anemia proteins implications in cancer predisposition |
| topic | Fanconi anemia DNA repair mitochondria cancers inflammation |
| url | https://www.mdpi.com/2072-6694/12/9/2684 |
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