Integrating Manipulatives and Animations to Visualize Holliday Junctions

Abstract

The complex molecular architecture of Holliday junctions is often challenging for undergraduate biochemistry students to conceptualize. In particular, they have difficulty translating from two-dimensional, linear representations shown in textbooks to the atomic-resolution DNA structures. This challenge impedes their comprehension of the mechanisms by which proteins are able to bind, hydrolyze, and re-ligate the component DNA strands. We have developed an affordable, portable Holliday junction model using colored chenille stems (a.k.a. pipe cleaners) that students use to first visualize the DNA structures within Holliday junctions, and relate those structures to the static two-dimensional representations in textbooks. To fully integrate the linear depictions with the three-dimensional models, students then watch an online animated movie that models the dynamics of Holliday junction resolution. Students then use those models to work problem sets that include questions about double-stranded break repair, mating-type switching, and genetic crossover. The implementation of these personal manipulative models for each student has notably improved student comprehension of the molecular mechanism of homologous recombination. <em>Primary image:&nbsp;</em>Representations of Holliday Junctions. Top row: a conventional line schematic of a Holliday junction, in which there are four heteroduplexes of double-stranded DNA, shown beside a cartoon representation of a Holliday junction solved by x-ray crystallography (PDB: 1DCW). Bottom row: a chenille-stem manipulative, which can be interconverted between the conventional line schematic and the open-cruciform structure that are depicted in the top row.