biostudies-literatureLormand JDNIEHS NIH HHSNIGMS NIH HHS10323-33https://www.ebi.ac.uk/biostudies/studies/S-EPMC3905856biostudies-literatureUnknown41(22)Previous evidence indicates that telomeres resemble common fragile sites and present a challenge for DNA replication. The precise impediments to replication fork progression at telomeric TTAGGG repeats are unknown, but are proposed to include G-quadruplexes (G4) on the G-rich strand. Here we examined DNA synthesis and progression by the replicative DNA polymerase δ/proliferating cell nuclear antigen/replication factor C complex on telomeric templates that mimic the leading C-rich and lagging G-rich strands. Increased polymerase stalling occurred on the G-rich template, compared with the C-rich and nontelomeric templates. Suppression of G4 formation by substituting Li(+) for K(+) as the cation, or by using templates with 7-deaza-G residues, did not alleviate Pol δ pause sites within the G rNucleic acids researchDNA polymerase δ stalls on telomeric lagging strand templates independently from G-quadruplex formation.PMC3905856R01GM031973R01ES0515052R00ES016758R01 GM065484R00 ES016758R01 ES015052R01GM032431Z01 ES065070Opresko PLBurgers PKunkel TALormand JDKaur PWang HLee MYBuncher NMurphy CTfalseDNA polymerase δ stalls on telomeric lagging strand templates independently from G-quadruplex formation.Previous evidence indicates that telomeres resemble common fragile sites and present a challenge for DNA replication. The precise impediments to replication fork progression at telomeric TTAGGG repeats are unknown, but are proposed to include G-quadruplexes (G4) on the G-rich strand. Here we examined DNA synthesis and progression by the replicative DNA polymerase δ/proliferating cell nuclear antigen/replication factor C complex on telomeric templates that mimic the leading C-rich and lagging G-rich strands. Increased polymerase stalling occurred on the G-rich template, compared with the C-rich and nontelomeric templates. Suppression of G4 formation by substituting Li(+) for K(+) as the cation, or by using templates with 7-deaza-G residues, did not alleviate Pol δ pause sites within the G r2013-01-01T00:00:00Z2013 Dec2025-04-22T19:27:09.299Z2019-03-27T01:20:50ZS-EPMC39058562403847010.1093/nar/gkt813