DNA DAMAGE RESPONSE, CHECKPOINT ACTIVATION AND DYSFUNCTIONAL TELOMERES: FACE TO FACE BETWEEN MAMMALIAN CELLS
AND DROSOPHILA
Francesca Cipressa, Giovanni Cenci
Dipartimento di Biologia e Biotenologie "C. Darwin"; Sapienza, Università di Roma, Italy;
e-mail: giovanni.cenci@uniroma1.it
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.
Key words: telomeres, DNA damage response, cell cycle checkpoint, mammals, Drosophila
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