Sit down, relax and unwind: structural insights into RecQ helicase mechanisms

Abstract

Helicases are specialized molecular motors that separate duplex nucleic acids into single strands. The RecQ family of helicases functions at the interface of DNA replication, recombination and repair in bacterial and eukaryotic cells. They are key, multifunctional enzymes that have been linked to three human diseases: Bloom's, Werner's and Rothmund-Thomson's syndromes. This review summarizes recent studies that relate the structures of RecQ proteins to their biochemical activities.

Figure 1

Schematic illustration of the structural or functional properties of RecQ protein domains. The N- and C-terminal extensions (gray) from the conserved core domains and the Helicase (red), RecQ-Ct (green) and HRDC (peach) domains are shown on the left-hand side. Boxes outlining contributions or deficiencies associated with each region are shown on the right-hand side in corresponding colors.

Figure 2

Structural features of RecQ DNA helicases. (a) Orthogonal views of a ribbon diagram of RecQ catalytic core crystal structure (31). The catalytic core domain is composed of the helicase domain shown in red and blue, and the RecQ-Ct domain shown in yellow and green. The ATPγS moiety is colored according to atom identity where carbon = slate, nitrogen = blue, oxygen = red, and phosphorus or sulfur = orange. (b) Stereo diagram of the ATP-binding site and residues predicted to be involved in hydrolysis. The main chain of the conserved motifs and their relevant residues are colored as follows: Motif 0 in purple, Motif I in green, Motif II in cyan and Motif VI in gold. An Mn²⁺ ion is shown as a purple sphere above Lys53. (c) Subdomains of the RecQ-Ct domain. The zinc-binding domain is shown in yellow, with the four Zn²⁺ coordinating cysteine residues shown in blue. The winged-helix domain is shown in green and contains the ‘recognition helix’. (d) The HRDC domain (32) is shown in salmon and its 3₁₀ helix is labeled. (e) Structure of the WRN exonuclease domain bound to Mg²⁺ (74). Helices (blue), sheets (red) and loops (salmon) are shown with active site residue sidechains as green sticks and Mg²⁺ ions as magenta spheres. Structure figures created using PyMol (79).