Fig. 2. Telomere replication. (A) Telomeres in all organisms contain a short 3' overhang on the G rich strand. (B) A replication fork moving towards the end of the chromosome. (C) The newly replicated, lagging C strand, will generate a natural 3' overhang when the RNA primer is removed from the final Okazaki fragment, or if the lagging strand replication machinery cannot reach the end of the chromosome. In the absence of nuclease activity the unreplicated 3' strand will be the same length as it was prior to replication. (D) The newly replicated leading G strand will be the same length as the parental 5' C strand, and blunt ended if the replication fork reaches the end of the chromosome. Therefore the newly replicated 3' G strand will be shorter than the parental 3' strand and unable to act as a substrate for telomerase because it does not contain a 3' overhang. If the leading strand replication fork does not reach the end of the chromosome a 5' rather than 3' overhang would be generated, but this would not be a suitable substrate for telomerase.