Abstract
Formation of crossovers between homologous chromosomes during Caenorhabditis elegans meiosis requires the him-14 gene. Loss of him-14 function severely reduces crossing over, resulting in lack of chiasmata between homologs and consequent missegregation. Cytological analysis showing that homologs are paired and aligned in him-14 pachytene nuclei, together with temperature-shift experiments showing that him-14 functions during the pachytene stage, indicate that him-14 is not needed to establish pairing or synapsis and likely has a more direct role in crossover formation. him-14 encodes a germline-specific member of the MutS family of DNA mismatch repair (MMR) proteins. him-14 has no apparent role in MMR, but like its Saccharomyces cerevisiae ortholog MSH4, has a specialized role in promoting crossing over during meiosis. Despite this conservation, worms and yeast differ significantly in their reliance on this pathway: whereas worms use this pathway to generate most, if not all, crossovers, yeast still form 30-50% of their normal number of crossovers when this pathway is absent. This differential reliance may reflect differential stability of crossover-competent recombination intermediates, or alternatively, the presence of two different pathways for crossover formation in yeast, only one of which predominates during nematode meiosis. We discuss a model in which HIM-14 promotes crossing over by interfering with Holliday junction branch migration.
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- Alani E., Sokolsky T., Studamire B., Miret J. J., Lahue R. S. Genetic and biochemical analysis of Msh2p-Msh6p: role of ATP hydrolysis and Msh2p-Msh6p subunit interactions in mismatch base pair recognition. Mol Cell Biol. 1997 May;17(5):2436–2447. doi: 10.1128/mcb.17.5.2436. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Alani E. The Saccharomyces cerevisiae Msh2 and Msh6 proteins form a complex that specifically binds to duplex oligonucleotides containing mismatched DNA base pairs. Mol Cell Biol. 1996 Oct;16(10):5604–5615. doi: 10.1128/mcb.16.10.5604. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Albertson D. G., Fishpool R. M., Birchall P. S. Fluorescence in situ hybridization for the detection of DNA and RNA. Methods Cell Biol. 1995;48:339–364. doi: 10.1016/s0091-679x(08)61395-3. [DOI] [PubMed] [Google Scholar]
- Barnes T. M., Kohara Y., Coulson A., Hekimi S. Meiotic recombination, noncoding DNA and genomic organization in Caenorhabditis elegans. Genetics. 1995 Sep;141(1):159–179. doi: 10.1093/genetics/141.1.159. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Blackwell L. J., Martik D., Bjornson K. P., Bjornson E. S., Modrich P. Nucleotide-promoted release of hMutSalpha from heteroduplex DNA is consistent with an ATP-dependent translocation mechanism. J Biol Chem. 1998 Nov 27;273(48):32055–32062. doi: 10.1074/jbc.273.48.32055. [DOI] [PubMed] [Google Scholar]
- Brenner S. The genetics of Caenorhabditis elegans. Genetics. 1974 May;77(1):71–94. doi: 10.1093/genetics/77.1.71. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Byers B., Goetsch L. Electron microscopic observations on the meiotic karyotype of diploid and tetraploid Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1975 Dec;72(12):5056–5060. doi: 10.1073/pnas.72.12.5056. [DOI] [PMC free article] [PubMed] [Google Scholar]
- C. elegans Sequencing Consortium Genome sequence of the nematode C. elegans: a platform for investigating biology. Science. 1998 Dec 11;282(5396):2012–2018. doi: 10.1126/science.282.5396.2012. [DOI] [PubMed] [Google Scholar]
- Chua P. R., Roeder G. S. Zip2, a meiosis-specific protein required for the initiation of chromosome synapsis. Cell. 1998 May 1;93(3):349–359. doi: 10.1016/s0092-8674(00)81164-2. [DOI] [PubMed] [Google Scholar]
- Dernburg A. F., McDonald K., Moulder G., Barstead R., Dresser M., Villeneuve A. M. Meiotic recombination in C. elegans initiates by a conserved mechanism and is dispensable for homologous chromosome synapsis. Cell. 1998 Aug 7;94(3):387–398. doi: 10.1016/s0092-8674(00)81481-6. [DOI] [PubMed] [Google Scholar]
- Dernburg A. F., Sedat J. W. Mapping three-dimensional chromosome architecture in situ. Methods Cell Biol. 1998;53:187–233. doi: 10.1016/s0091-679x(08)60880-8. [DOI] [PubMed] [Google Scholar]
- Edgar L. G. Blastomere culture and analysis. Methods Cell Biol. 1995;48:303–321. doi: 10.1016/s0091-679x(08)61393-x. [DOI] [PubMed] [Google Scholar]
- Gilbertson L. A., Stahl F. W. A test of the double-strand break repair model for meiotic recombination in Saccharomyces cerevisiae. Genetics. 1996 Sep;144(1):27–41. doi: 10.1093/genetics/144.1.27. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goldstein P., Slaton D. E. The synaptonemal complexes of caenorhabditis elegans: comparison of wild-type and mutant strains and pachytene karyotype analysis of wild-type. Chromosoma. 1982;84(4):585–597. doi: 10.1007/BF00292857. [DOI] [PubMed] [Google Scholar]
- Gradia S., Subramanian D., Wilson T., Acharya S., Makhov A., Griffith J., Fishel R. hMSH2-hMSH6 forms a hydrolysis-independent sliding clamp on mismatched DNA. Mol Cell. 1999 Feb;3(2):255–261. doi: 10.1016/s1097-2765(00)80316-0. [DOI] [PubMed] [Google Scholar]
- Gumienny T. L., Lambie E., Hartwieg E., Horvitz H. R., Hengartner M. O. Genetic control of programmed cell death in the Caenorhabditis elegans hermaphrodite germline. Development. 1999 Feb;126(5):1011–1022. doi: 10.1242/dev.126.5.1011. [DOI] [PubMed] [Google Scholar]
- Hodgkin J., Horvitz H. R., Brenner S. Nondisjunction Mutants of the Nematode CAENORHABDITIS ELEGANS. Genetics. 1979 Jan;91(1):67–94. doi: 10.1093/genetics/91.1.67. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hollingsworth N. M., Ponte L., Halsey C. MSH5, a novel MutS homolog, facilitates meiotic reciprocal recombination between homologs in Saccharomyces cerevisiae but not mismatch repair. Genes Dev. 1995 Jul 15;9(14):1728–1739. doi: 10.1101/gad.9.14.1728. [DOI] [PubMed] [Google Scholar]
- Hunter N., Borts R. H. Mlh1 is unique among mismatch repair proteins in its ability to promote crossing-over during meiosis. Genes Dev. 1997 Jun 15;11(12):1573–1582. doi: 10.1101/gad.11.12.1573. [DOI] [PubMed] [Google Scholar]
- Keeney S., Giroux C. N., Kleckner N. Meiosis-specific DNA double-strand breaks are catalyzed by Spo11, a member of a widely conserved protein family. Cell. 1997 Feb 7;88(3):375–384. doi: 10.1016/s0092-8674(00)81876-0. [DOI] [PubMed] [Google Scholar]
- Kemphues K. J., Kusch M., Wolf N. Maternal-effect lethal mutations on linkage group II of Caenorhabditis elegans. Genetics. 1988 Dec;120(4):977–986. doi: 10.1093/genetics/120.4.977. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kleckner N. Meiosis: how could it work? Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8167–8174. doi: 10.1073/pnas.93.16.8167. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kohara Y. [Large scale analysis of C. elegans cDNA]. Tanpakushitsu Kakusan Koso. 1996 Apr;41(5):715–720. [PubMed] [Google Scholar]
- Labouesse M., Sookhareea S., Horvitz H. R. The Caenorhabditis elegans gene lin-26 is required to specify the fates of hypodermal cells and encodes a presumptive zinc-finger transcription factor. Development. 1994 Sep;120(9):2359–2368. doi: 10.1242/dev.120.9.2359. [DOI] [PubMed] [Google Scholar]
- McKim K. S., Green-Marroquin B. L., Sekelsky J. J., Chin G., Steinberg C., Khodosh R., Hawley R. S. Meiotic synapsis in the absence of recombination. Science. 1998 Feb 6;279(5352):876–878. doi: 10.1126/science.279.5352.876. [DOI] [PubMed] [Google Scholar]
- McKim K. S., Hayashi-Hagihara A. mei-W68 in Drosophila melanogaster encodes a Spo11 homolog: evidence that the mechanism for initiating meiotic recombination is conserved. Genes Dev. 1998 Sep 15;12(18):2932–2942. doi: 10.1101/gad.12.18.2932. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Paquis-Flucklinger V., Santucci-Darmanin S., Paul R., Saunières A., Turc-Carel C., Desnuelle C. Cloning and expression analysis of a meiosis-specific MutS homolog: the human MSH4 gene. Genomics. 1997 Sep 1;44(2):188–194. doi: 10.1006/geno.1997.4857. [DOI] [PubMed] [Google Scholar]
- Pochart P., Woltering D., Hollingsworth N. M. Conserved properties between functionally distinct MutS homologs in yeast. J Biol Chem. 1997 Nov 28;272(48):30345–30349. doi: 10.1074/jbc.272.48.30345. [DOI] [PubMed] [Google Scholar]
- Rockmill B., Sym M., Scherthan H., Roeder G. S. Roles for two RecA homologs in promoting meiotic chromosome synapsis. Genes Dev. 1995 Nov 1;9(21):2684–2695. doi: 10.1101/gad.9.21.2684. [DOI] [PubMed] [Google Scholar]
- Roeder G. S. Meiotic chromosomes: it takes two to tango. Genes Dev. 1997 Oct 15;11(20):2600–2621. doi: 10.1101/gad.11.20.2600. [DOI] [PubMed] [Google Scholar]
- Ross-Macdonald P., Roeder G. S. Mutation of a meiosis-specific MutS homolog decreases crossing over but not mismatch correction. Cell. 1994 Dec 16;79(6):1069–1080. doi: 10.1016/0092-8674(94)90037-x. [DOI] [PubMed] [Google Scholar]
- Sym M., Roeder G. S. Crossover interference is abolished in the absence of a synaptonemal complex protein. Cell. 1994 Oct 21;79(2):283–292. doi: 10.1016/0092-8674(94)90197-x. [DOI] [PubMed] [Google Scholar]
- Telenius H., Carter N. P., Bebb C. E., Nordenskjöld M., Ponder B. A., Tunnacliffe A. Degenerate oligonucleotide-primed PCR: general amplification of target DNA by a single degenerate primer. Genomics. 1992 Jul;13(3):718–725. doi: 10.1016/0888-7543(92)90147-k. [DOI] [PubMed] [Google Scholar]
- Villeneuve A. M. A cis-acting locus that promotes crossing over between X chromosomes in Caenorhabditis elegans. Genetics. 1994 Mar;136(3):887–902. doi: 10.1093/genetics/136.3.887. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vollrath D., Davis R. W. Resolution of DNA molecules greater than 5 megabases by contour-clamped homogeneous electric fields. Nucleic Acids Res. 1987 Oct 12;15(19):7865–7876. doi: 10.1093/nar/15.19.7865. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Weiner B. M., Kleckner N. Chromosome pairing via multiple interstitial interactions before and during meiosis in yeast. Cell. 1994 Jul 1;77(7):977–991. doi: 10.1016/0092-8674(94)90438-3. [DOI] [PubMed] [Google Scholar]
- Williams B. D., Schrank B., Huynh C., Shownkeen R., Waterston R. H. A genetic mapping system in Caenorhabditis elegans based on polymorphic sequence-tagged sites. Genetics. 1992 Jul;131(3):609–624. doi: 10.1093/genetics/131.3.609. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zetka M. C., Rose A. M. Mutant rec-1 eliminates the meiotic pattern of crossing over in Caenorhabditis elegans. Genetics. 1995 Dec;141(4):1339–1349. doi: 10.1093/genetics/141.4.1339. [DOI] [PMC free article] [PubMed] [Google Scholar]