Sequence-dependent DNA flexibility mediates DNase I cleavage.

Brahim Heddi (1) , Josephine Abi-Ghanem (2) , Marc Lavigne (3) , Brigitte Hartmann (1)

1 IBPC (FR_550) - Institut de biologie physico-chimique
2 INSERM UMR S665
3 Virologie Structurale

Understanding the preference of nonspecific proteins for certain DNA structural features requires an accurate description of the properties of free DNA, especially regarding their possible predisposition to adopt a conformation that favors the formation of a complex. Exploiting previous exhaustive NMR studies performed on free DNA oligomers, we investigated the molecular basis of DNase I sensitivity under conditions where DNase I binding limits the probability of cleavage. We showed that cleavage intensity was correlated with adjacent 3' phosphate linkage flexibility, monitored by (31)P chemical shifts. Examining NMR-refined DNA structures highlighted that sequence-dependent flexible phosphates were associated with large minor groove variations that may promote the affinity of DNase I, according to relevant DNA-protein complexes. In sum, this work demonstrates that specificity in DNA-DNase I interaction is mediated by DNA flexibility, which influences the induced-fit transitions required to form productive complexes.

Keywords: DNA–protein nonspecific interaction; DNase I cleavage specificity; DNA flexibility; BI ↔ BII equilibrium; 31 P chemical shifts

Domains: Life Sciences [q-bio]; Biochemistry, Molecular Biology; Biochemistry [q-bio.BM]; Life Sciences [q-bio]; Biochemistry, Molecular Biology; Structural Biology [q-bio.BM]

Brahim Heddi, Josephine Abi-Ghanem, Marc Lavigne, Brigitte Hartmann. Sequence-dependent DNA flexibility mediates DNase I cleavage.. Journal of Molecular Biology, 2010, 395 (1), pp.123-33. ⟨10.1016/j.jmb.2009.10.023⟩. ⟨pasteur-01416864⟩