Fig. 2

A “looping–out” mechanism to resolve a stalled replication fork at telomeres via the topoisomerase II (Topo–II) and NHEJ mechanism. Unresolved G–quadruplex (G4) structures hinder completion of DNA replication at telomeric regions. Topo–II cleavages on both sides release the stalled replication fork and generate both leading and lagging daughter DNA. Repair and ligation via the NHEJ, HR or other repair mechanisms support replication, which resumes at newly ligated telomeres, causing the production of T–circles from the released leading and lagging DNA. The T–circles progress into T–circle–tail or single–stranded C–circles, which could participate in telomere extension through the ALT mechanism. This figure is modified from Zeng et al., EMBO Rep 18: 1412–1428