BLM helicase facilitates telomere replication during leading strand synthesis of telomeres

William C. Drosopoulos, Settapong T. Kosiyatrakul, Carl L. Schildkraut

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

Based on its in vitro unwinding activity on G-quadruplex (G4) DNA, the Bloom syndrome-associated helicase BLM is proposed to participate in telomere replication by aiding fork progression through G-rich telomeric DNA. Single molecule analysis of replicated DNA (SMARD) was used to determine the contribution of BLM helicase to telomere replication. In BLM-deficient cells, replication forks initiating from origins within the telomere, which copy the G-rich strand by leading strand synthesis, moved slower through the telomere compared with the adjacent subtelomere. Fork progression through the telomere was further slowed in the presence of a G4 stabilizer. Using a G4-specific antibody, we found that deficiency of BLM, or another G4-unwinding helicase, the Werner syndrome-associated helicase WRN, resulted in increased G4 structures in cells. Importantly, deficiency of either helicase led to greater increases in G4 DNA detected in the telomere compared with G4 seen genome-wide. Collectively, our findings are consistent with BLM helicase facilitating telomere replication by resolving G4 structures formed during copying of the G-rich strand by leading strand synthesis.

Original languageEnglish (US)
Pages (from-to)191-208
Number of pages18
JournalJournal of Cell Biology
Volume210
Issue number2
DOIs
StatePublished - 2015

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Telomere
DNA
Bloom Syndrome
G-Quadruplexes
Genome
Antibodies

ASJC Scopus subject areas

  • Cell Biology

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BLM helicase facilitates telomere replication during leading strand synthesis of telomeres. / Drosopoulos, William C.; Kosiyatrakul, Settapong T.; Schildkraut, Carl L.

In: Journal of Cell Biology, Vol. 210, No. 2, 2015, p. 191-208.

Research output: Contribution to journalArticle

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