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Genetics. 2014 Sep;198(1):193-207. doi: 10.1534/genetics.114.161513. Epub 2014 Jul 21.

DNA helicase HIM-6/BLM both promotes MutSγ-dependent crossovers and antagonizes MutSγ-independent interhomolog associations during caenorhabditis elegans meiosis.

Author information

1
Departments of Developmental Biology and Genetics, Stanford University School of Medicine, Stanford, California 94305.
2
Department of Cell and Developmental Biology, University of Michigan Medical School, Ann Arbor, Michigan 48109-2200.
3
MRC Clinical Sciences Centre, Imperial College Faculty of Medicine, London, United Kingdom.
4
Department of Biology, Geology, Environmental Science, Cleveland State University, Cleveland, Ohio 44115.
5
Howard Hughes Medical Institute and Department of Molecular and Cell Biology, University of California, Berkeley, California 94720.
6
Departments of Developmental Biology and Genetics, Stanford University School of Medicine, Stanford, California 94305 annev@stanford.edu.

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.

KEYWORDS:

BLM helicase; Caenorhabditis elegans; MutSγ; meiosis; recombination

PMID:
25053665
PMCID:
PMC4174932
DOI:
10.1534/genetics.114.161513
[Indexed for MEDLINE]
Free PMC Article

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