The role of Q motif in superfamily 2 DNA helicases

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DNA helicases are ATP-dependent motor proteins that unwind duplex DNA to form single stranded DNA intermediates that are required for DNA metabolism in all organisms. Superfamily 2 (SF2) is the largest of six helicase families. The conversion of energy derived from ATP hydrolysis into unwinding of double-stranded nucleic acids is coordinated by seven sequence motifs (I, Ia, II, III, IV, V, and VI). The Q motif is located upstream of motif I and consists of a nine amino acid sequence (GFXXPXPIQ) containing an invariant glutamine (Q) residue. Although increasing evidences suggest that the Q motif is essential for helicase function, the role of Q motif is less appreciated compared with the seven conserved helicase motifs. Our biochemical and genetic analyses demonstrate that the Q motif in FANCJ helicase is essential for its helicase activity and DNA repair function in vivo by regulation of the dimerization of FANCJ protein, which is a novel function for the Q motif. It remains unknown whether such function is conserved in FANCJ-like helicases (ChlR1 and RTEL1) and the RecQ helicase family, which all contain the Q motif in their primary sequence. Using a combination of structural, biochemical, and cellular approaches, our studies aim to 1) Continue to define the role of the Q motif in the FANCJ helicase, 2) Examine the role of the Q motif in the FANCJ-like helicases ChlR1 and RTEL1, and 3) Determine the functional and structural roles of the Q motif in the RecQ helicase family. The results obtained from this study will advance fundamental knowledge of structural elements of SF2 DNA helicases, which play vital roles in DNA replication, repair, recombination, transcription, chromosome segregation, and telomere maintenance that conserved from archaea, bacteria, to eukaryotes.