Author/Authors :
Jing Ye، نويسنده , , Christelle Lenain، نويسنده , , Serge Bauwens، نويسنده , , Angela Rizzo، نويسنده , , Adelaïde Saint-Léger، نويسنده , , Anaïs Poulet، نويسنده , , Delphine Benarroch، نويسنده , , Frédérique Magdinier، نويسنده , , Julia Morere، نويسنده , , Simon Amiard، نويسنده , , Els Verhoeyen، نويسنده , , Sébastien Britton، نويسنده , , Patrick Calsou، نويسنده , , Bernard Salles، نويسنده , , Anna Bizard، نويسنده , , Marc Nadal، نويسنده , , Erica Salvati، نويسنده , , Laure Sabatier، نويسنده , , Yunlin Wu، نويسنده , , Annamaria Biroccio، نويسنده , , et al.، نويسنده ,
Abstract :
Human telomeres are protected from DNA damage by a nucleoprotein complex that includes the repeat-binding factor TRF2. Here, we report that TRF2 regulates the 5′ exonuclease activity of its binding partner, Apollo, a member of the metallo-β-lactamase family that is required for telomere integrity during S phase. TRF2 and Apollo also suppress damage to engineered interstitial telomere repeat tracts that were inserted far away from chromosome ends. Genetic data indicate that DNA topoisomerase 2α acts in the same pathway of telomere protection as TRF2 and Apollo. Moreover, TRF2, which binds preferentially to positively supercoiled DNA substrates, together with Apollo, negatively regulates the amount of TOP1, TOP2α, and TOP2β at telomeres. Our data are consistent with a model in which TRF2 and Apollo relieve topological stress during telomere replication. Our work also suggests that cellular senescence may be caused by topological problems that occur during the replication of the inner portion of telomeres.
