DNA Helicase HIM-6/BLM Both Promotes MutSγ-Dependent Crossovers and Antagonizes MutSγ-Independent Inter-Homolog Associations During Caenorhabditis elegans Meiosis
Mara Schvarzstein, Divya Pattabiraman, Diana E. Libuda, Ajit Ramadugu, Angela Tam, Enrique Martinez-Perez, Baptiste Roelens, Karl A. Zawadzki, Rayka Yokoo, Simona Rosu, Aaron F. Severson, Barbara J. Meyer, Kentaro Nabeshima, Anne M. Villeneuve

Abstract

Meiotic recombination is initiated by the programmed induction of double-strand DNA breaks (DSBs), lesions that pose a potential threat to the genome. A subset of the DSBs induced during meiotic prophase become designated to be repaired by a pathway that specifically yields inter-homolog crossovers (COs), which mature into chiasmata that temporarily connect the homologs to ensure their proper segregation at meiosis I. The remaining DSBs must be repaired by other mechanisms to restore genomic integrity prior to the meiotic divisions. Here we show that HIM-6, the Caenorhabditis elegans ortholog of the RecQ family DNA helicase BLM, functions in both of these processes. We show that him-6 mutants are competent to load the MutSγ complex at multiple potential CO sites, to generate intermediates that fulfill the requirements of monitoring mechanisms that enable meiotic progression, and to accomplish and robustly regulate CO designation. However, recombination events at a subset of CO-designated sites fail to mature into COs and chiasmata, indicating a pro-CO role for HIM-6/BLM that manifests itself late in the CO pathway. Moreover, we find that in addition to promoting COs, HIM-6 also plays a role in eliminating and/or preventing the formation of persistent MutSγ-independent associations between homologous chromosomes. We propose that HIM-6/BLM enforces biased outcomes of recombination events to ensure both that a) CO-designated recombination intermediates are reliably resolved as COs and b) other recombination intermediates reliably mature into non-crossovers in a timely manner.

  • Received January 13, 2014.
  • Accepted July 14, 2014.