title: DNA helicase HIM-6/BLM both promotes MutSγ-dependent crossovers and antagonizes MutSγ-independent interhomolog associations during caenorhabditis elegans meiosis.
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 interhomolog 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 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 that both (a) CO-designated recombination intermediates are reliably resolved as COs and (b) other recombination intermediates reliably mature into noncrossovers in a timely manner.
authors: Departments of Developmental Biology and Genetics, Stanford University School of Medicine, Stanford, California 94305.
authors: Mara
authors: M
authors: Schvarzstein
authors: Departments of Developmental Biology and Genetics, Stanford University School of Medicine, Stanford, California 94305.
authors: Divya
authors: D
authors: Pattabiraman
authors: Departments of Developmental Biology and Genetics, Stanford University School of Medicine, Stanford, California 94305.
authors: Diana E
authors: DE
authors: Libuda
authors: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan 48109-2200.
authors: Ajit
authors: A
authors: Ramadugu
authors: Departments of Developmental Biology and Genetics, Stanford University School of Medicine, Stanford, California 94305.
authors: Angela
authors: A
authors: Tam
authors: MRC Clinical Sciences Centre, Imperial College Faculty of Medicine, London, United Kingdom.
authors: Enrique
authors: E
authors: Martinez-Perez
authors: Departments of Developmental Biology and Genetics, Stanford University School of Medicine, Stanford, California 94305.
authors: Baptiste
authors: B
authors: Roelens
authors: Departments of Developmental Biology and Genetics, Stanford University School of Medicine, Stanford, California 94305.
authors: Karl A
authors: KA
authors: Zawadzki
authors: Departments of Developmental Biology and Genetics, Stanford University School of Medicine, Stanford, California 94305.
authors: Rayka
authors: R
authors: Yokoo
authors: Departments of Developmental Biology and Genetics, Stanford University School of Medicine, Stanford, California 94305.
authors: Simona
authors: S
authors: Rosu
authors: Department of Biology, Geology, Environmental Science, Cleveland State University, Cleveland, Ohio 44115.
authors: Aaron F
authors: AF
authors: Severson
authors: Howard Hughes Medical Institute and Department of Molecular and Cell Biology, University of California, Berkeley, California 94720.
authors: Barbara J
authors: BJ
authors: Meyer
authors: Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan 48109-2200.
authors: Kentaro
authors: K
authors: Nabeshima
authors: Departments of Developmental Biology and Genetics, Stanford University School of Medicine, Stanford, California 94305 annev@stanford.edu.
authors: Anne M
authors: AM
authors: Villeneuve
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000201:enzymology / Q000235:genetics*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism*; D003434:Crossing Over, Genetic; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D008540:Meiosis / Q000235:genetics
chemical_list: D029742:Caenorhabditis elegans Proteins; D004268:DNA-Binding Proteins; C487047:HIM-6 protein, C elegans; C552835:MSH-5 protein, C elegans
keywords: BLM helicase; Caenorhabditis elegans; MutSγ; meiosis; recombination