Fanconi anemia proteins in telomere maintenance.
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.
Laboratory of Molecular Gerontology, National Institute on Aging/National Institutes of Health, 251 Bayview Blvd, Baltimore, MD 21044, USA.
Jaya
J
Sarkar
Laboratory of Molecular Gerontology, National Institute on Aging/National Institutes of Health, 251 Bayview Blvd, Baltimore, MD 21044, USA. Electronic address: liuyie@mail.nih.gov.
Yie
Y
Liu
D000818:Animals; D002877:Chromosomes, Human / Q000737:chemistry / Q000378:metabolism; D004247:DNA / Q000235:genetics* / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded; D004260:DNA Repair; D004261:DNA Replication; D005199:Fanconi Anemia / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D051856:Fanconi Anemia Complementation Group Proteins / Q000235:genetics* / Q000378:metabolism; D042822:Genomic Instability; D006801:Humans; D009690:Nucleic Acid Conformation; D000089804:Shelterin Complex; D016615:Telomere / Q000737:chemistry / Q000378:metabolism*; D059505:Telomere Homeostasis; D034501:Telomere-Binding Proteins / Q000235:genetics* / Q000378:metabolism
D051856:Fanconi Anemia Complementation Group Proteins; D000089804:Shelterin Complex; D034501:Telomere-Binding Proteins; D004247:DNA
DNA joint Molecule intermediates; DNA repair; Fanconi anemia; Telomere maintenance