A conserved G4 DNA binding domain in RecQ family helicases

RecQ family helicases play important roles at G-rich domains of the genome, including the telomeres, rDNA, and immunoglobulin switch regions. This appears to reflect the unusual ability of enzymes in this family to unwind G4 DNA. How RecQ family helicases recognize this substrate has not been established. Here, we show that G4 DNA is a preferred target for BLM helicase within the context of long DNA molecules. We identify the RQC domain, found only in RecQ family enzymes, as an independent, high affinity and conserved G4 DNA binding domain; and show that binding to Holliday junctions involves both the RQC and the HRDC domains. These results provide mechanistic understanding of differences and redundancies of function and activities among RecQ family helicases, and of how deficiencies in human members of this family may contribute to genomic instability and disease.