Functional links between telomeres and proteins of the DNA-damage response

In response to DNA damage, cells engage a complex set of events that together comprise the DNA-damage response (DDR). These events bring about the repair of the damage and also slow down or halt cell cycle progression until the damage has been removed. In stark contrast, the ends of linear chromosomes, telomeres, are generally not perceived as DNA damage by the cell even though they terminate the DNA double-helix. Nevertheless, it has become clear over the past few years that many proteins involved in the DDR, particularly those involved in responding to DNA double-strand breaks, also play key roles in telomere maintenance. In this review, we discuss the current knowledge of both the telomere and the DDR, and then propose an integrated model for the events associated with the metabolism of DNA ends in these two distinct physiological contexts.