Bloom helicase contributes to successful crossover formation with both catalytic and structural roles in Caenorhabditis elegans meiosis

Authors:

Sowmya Sivakumar Geetha, Ivana Čavka, Maria Rosaria Dello Stritto, Angela Graf, Tomas Macha, Hannah Krakolinig, Simone Köhler, Verena Jantsch

Keywords:

Crossover; meiosis; DNA double-strand break; chromosome segregation; Bloom-Topoisomerase 3–RMI1/2 complex; Bloom helicase; HIM-6; C. elegans

Abstract:

Crossover (CO)-biased repair of meiotic DNA double-strand breaks is essential for proper chromosome segregation. However, only a subset of programmed induced DSBs is repaired as COs, while the rest is processed into non-COs. The Bloom-Topoisomerase 3–RMI1/2 complex is well documented to disassemble joint recombination intermediates into non-COs, but its pro-CO activities are less well understood. Here, we investigate how the pro-CO activities of the Caenorhabditis elegans Bloom helicase ortholog HIM-6 contribute to meiotic recombination by studying a catalytically inactive mutant. We show that HIM-6 helicase activity is required to provide a continuous flux of substrates for CO formation, probably via its unwinding activities, and that a structural role is sufficient to channel intermediates into the preferred pathway to generate correctly positioned COs. We provide evidence that the catalytic activity of Bloom helicase influences the geometry of the joint DNA molecules (double Holliday junctions (dHJ)). Localization of the signal for the dHJ-stabilizing complex MutSγ was more restricted, and epistasis experiments suggest that an altered geometry impedes the efficient processing of joint DNA molecules to generate CO-biased cleavage products.

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