Fanconi anemia proteins in telomere maintenance |
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| Institution: | 1. Department of Pathology and Laboratory Medicine, Weill Cornell Medicine, New York, NY 10065, USA;1. Section of Hematology/Oncology and Center for Clinical Cancer Genetics;2. Section of Pulmonary and Critical Care, Department of Medicine, The University of Chicago, Chicago, IL;;3. Center for Medical Genetics, NorthShore University HealthSystem, Evanston, IL;;4. UT Southwestern Medical Center, Dallas, TX;;5. Princess Margaret Cancer Centre, Department of Medicine, and;6. University Health Network, University of Toronto, Toronto, ON, Canada;;7. Department of Internal Medicine, School of Medicine, Yale University, New Haven, CT;;8. Section of Hematology, Department of Medicine, Stanford University Cancer Center, Stanford, CA;;9. Department of Pathology and Genomic Medicine, Houston Methodist Research Institute and Houston Methodist Hospital, Houston, TX;;10. Department of Human Genetics, The University of Chicago, Chicago, IL;;11. Department of Medicine and;12. Department of Genome Sciences, University of Washington, Seattle, WA; and;13. Department of Pathology, The University of Chicago, Chicago, IL;1. Department of Hematology, Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, Kanazawa, Japan;;2. Department of Clinical Laboratory Sciences, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan;;3. Department of Bioinformatics and Genomics, Graduate School of Advanced Preventive Medical Sciences, Kanazawa University, Kanazawa, Japan;;4. Pathology and Tumor Biology, Graduate School of Medicine, Kyoto University, Kyoto, Japan;1. Institute of Hematology and Medical Oncology “L.&A. Seragnoli,” University of Bologna, Bologna, Italy;2. Institute for Molecular Medicine, Goethe University, Frankfurt am Main, Germany;3. Section of Hematology/Oncology, University of Illinois at Chicago, Chicago, IL;4. University of Illinois at Chicago Cancer Center, University of Illinois at Chicago, Chicago, IL |
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| Abstract: | Mammalian chromosome ends are protected by nucleoprotein structures called telomeres. Telomeres ensure genome stability by preventing chromosome termini from being recognized as DNA damage. Telomere length homeostasis is inevitable for telomere maintenance because critical shortening or over-lengthening of telomeres may lead to DNA damage response or delay in DNA replication, and hence genome instability. Due to their repetitive DNA sequence, unique architecture, bound shelterin proteins, and high propensity to form alternate/secondary DNA structures, telomeres are like common fragile sites and pose an inherent challenge to the progression of DNA replication, repair, and recombination apparatus. It is conceivable that longer the telomeres are, greater is the severity of such challenges. Recent studies have linked excessively long telomeres with increased tumorigenesis. Here we discuss telomere abnormalities in a rare recessive chromosomal instability disorder called Fanconi Anemia and the role of the Fanconi Anemia pathway in telomere biology. Reports suggest that Fanconi Anemia proteins play a role in maintaining long telomeres, including processing telomeric joint molecule intermediates. We speculate that ablation of the Fanconi Anemia pathway would lead to inadequate aberrant structural barrier resolution at excessively long telomeres, thereby causing replicative burden on the cell. |
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| Keywords: | Telomere maintenance Fanconi anemia DNA repair DNA joint Molecule intermediates |
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