Replicating through telomeres: a means to an end

Proper replication of the telomeric DNA at chromosome ends is critical for preserving genome integrity. Yet, telomeres present challenges for the replication machinery, such as their repetitive and heterochromatic nature and their potential to form non-Watson-Crick structures as well as the fact that they are transcribed. Numerous telomere-bound proteins are required to facilitate progression of the replication fork throughout telomeric DNA. In particular, shelterin plays crucial functions in telomere length regulation, protection of telomeres from nuclease degradation, control of DNA damage response at telomeres, and the recruitment of associated factors required for telomere DNA processing and replication. In this review we discuss the recently uncovered functions of mammalian telomere-specific and telomere-associated proteins that facilitate proper telomere replication.