Possible mechanisms for replication-coupled telomere synthesis by telomerase in <i>CDC9</i> and <i>cdc9-1</i> cells.

<p>Grey bars and grey circles depict non-telomeric DNA and origins of replication within it respectively, whereas black bars correspond to telomeres. Green arrows represent telomerase activity coupled to conventional DNA replication whereas red arrows indicate telomerase action coordinated with BIR. In wild-type cells (see schematic at left), telomerase-dependent telomere elongation is coupled to conventional DNA replication of telomeric repeats (green arrow). In <i>cdc9-1</i> cells, nicks are present and replication through a nick would generate a broken replication fork with the remainder of the chromosome either not replicated, when there is no active <i>ARS</i> between the nick and a telomere (middle schematic), or replicated if replication is initiated within the region (schematic at right). The firing of replication origins (<i>ARS</i>) results in a passage of a conventional replication fork through the telomere (green arrow at right) and may be accompanied by telomere elongation by telomerase. However, the broken telomere-containing arm may be degraded/not involved in the repair of the broken DNA end on the other arm. Thus, in both cases, the repair in <i>cdc9-1</i> cells would proceed in a similar manner, via initiation of BIR that results in BIR-coupled action of telomerase at telomeres (red arrows). The telomeres in <i>cdc9-1</i> cells could be longer than in wild-type cells because the BIR-coupled telomerase activity (red arrows) is higher than when it is coordinated with conventional replication. Another possibility is that during BIR telomerase is provided with two windows of opportunity (the pathway on the right): one is when a conventional replication fork passes through a telomere (green arrow) and the other one is when the same telomere is replicated again by BIR (red arrow).