Journal
NUCLEIC ACIDS RESEARCH
Volume 30, Issue 18, Pages 3954-3961Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkf530
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Funding
- NCI NIH HHS [P01 CA16038, P01 CA016038] Funding Source: Medline
- NIGMS NIH HHS [R01 GM39799, R01 GM065988, R01 GM039799] Funding Source: Medline
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To understand the specific genetic instabilities associated with deficiencies in RecQ family helicases, we have studied the substrate preferences of two closely related members of this family, human BLM and Saccharomyces cerevisiae Sgs1p. Here we show that both BLM and Sgs1p preferentially unwind G4 DNA relative to Holliday junction substrates, and that substrate preference reflects binding affinity and maps to the conserved central helicase domain. We identify the porphyrin N-methyl mesoporphyrin IX (NMM) as a specific inhibitor of G4 DNA unwinding, and show that in the presence of NMM the helicase becomes trapped on the NMM-G4 DNA complex, consuming ATP but unable to unwind or dissociate. These results suggest that BLM and Sgs1p function proactively in replication to remove G4 DNA structures which would otherwise present obstacles to fork progression, rather than by promoting recombination to restart a fork that has stalled.
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