title: DNA damage response, checkpoint activation and dysfunctional telomeres: face to face between mammalian cells and Drosophila.
abstract: Eukaryotic cells evolved telomeres, specialized nucleoproteic complexes, to protect and replicate chromosome ends. In most organisms, telomeres consist of short, repetitive G-rich sequences added to chromosome ends by a reverse transcriptase with an internal RNA template, called telomerase. Specific DNA-binding protein complexes associate with telomeric sequences allowing cells to distinguish chromosome ends from sites of DNA damage. When telomeres become dysfunctional, either through excessive shortening or due to defects in the proteins that form their structure, they trigger p53/pRb pathways that limits proliferative lifespan and eventually leads to chromosome instability. Drosophila lacks telomerase, telomeres are assembled in a sequence-independent fashion and their length is maintained by transposition of three specialized retroelements. Nevertheless, fly telomeres are maintained by a number of proteins involved in telomere metabolism as in other eukaryotic systems and that are required to prevent checkpoint activation and end-to-end fusion. Uncapped Drosophila telomeres induce a DNA damage response just as dysfunctional human telomeres. Most interestingly, uncapped Drosophila telomeres also activate the spindle assembly checkpoint (SAC) by recruiting the SAC kinase BubR1. Here we review parallelisms and variations between mammalian and Drosophila cells in the crosstalks between telomeres and cell cycle regulation.
authors.affiliation: Dipartimento di Biologia e Biotecnologie "C. Darwin", Sapienza, Università di Roma, Italy.
authors.forename: F
authors.initials: F
authors.lastname: Cipressa
authors.forename: G
authors.initials: G
authors.lastname: Cenci
mesh_terms: D000818:Animals; D059447:Cell Cycle Checkpoints / Q000235:genetics*; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000378:metabolism; D004249:DNA Damage; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D016160:Retinoblastoma Protein / Q000235:genetics / Q000378:metabolism; D018626:Retroelements; D015398:Signal Transduction; D019098:Telomerase / Q000235:genetics / Q000378:metabolism; D016615:Telomere / Q000235:genetics* / Q000378:metabolism; D059505:Telomere Homeostasis; D034501:Telomere-Binding Proteins / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: C506005:BubR1 protein, Drosophila; D018797:Cell Cycle Proteins; D029721:Drosophila Proteins; D016160:Retinoblastoma Protein; D018626:Retroelements; D034501:Telomere-Binding Proteins; D016159:Tumor Suppressor Protein p53; D019098:Telomerase