XB-ART-45563
Nucleic Acids Res
2012 Sep 01;4017:8309-24. doi: 10.1093/nar/gks591.
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The N-terminus of the human RecQL4 helicase is a homeodomain-like DNA interaction motif.
Ohlenschläger O
,
Kuhnert A
,
Schneider A
,
Haumann S
,
Bellstedt P
,
Keller H
,
Saluz HP
,
Hortschansky P
,
Hänel F
,
Grosse F
,
Görlach M
,
Pospiech H
.
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The RecQL4 helicase is involved in the maintenance of genome integrity and DNA replication. Mutations in the human RecQL4 gene cause the Rothmund-Thomson, RAPADILINO and Baller-Gerold syndromes. Mouse models and experiments in human and Xenopus have proven the N-terminal part of RecQL4 to be vital for cell growth. We have identified the first 54 amino acids of RecQL4 (RecQL4_N54) as the minimum interaction region with human TopBP1. The solution structure of RecQL4_N54 was determined by heteronuclear liquid-state nuclear magnetic resonance (NMR) spectroscopy (PDB 2KMU; backbone root-mean-square deviation 0.73 Å). Despite low-sequence homology, the well-defined structure carries an overall helical fold similar to homeodomain DNA-binding proteins but lacks their archetypical, minor groove-binding N-terminal extension. Sequence comparison indicates that this N-terminal homeodomain-like fold is a common hallmark of metazoan RecQL4 and yeast Sld2 DNA replication initiation factors. RecQL4_N54 binds DNA without noticeable sequence specificity yet with apparent preference for branched over double-stranded (ds) or single-stranded (ss) DNA. NMR chemical shift perturbation observed upon titration with Y-shaped, ssDNA and dsDNA shows a major contribution of helix α3 to DNA binding, and additional arginine side chain interactions for the ss and Y-shaped DNA.
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Species referenced: Xenopus
Genes referenced: lgals4.2 recql4 spr topbp1
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