Caenorhabditis elegans msh-5 Is Required for Both Normal and Radiation-Induced Meiotic Crossing Over but Not for Completion of Meiosis

Corresponding author: Anne M. Villeneuve, Department of Developmental Biology, Stanford University School of Medicine, 279 Campus Dr., Beckman Center, B300, Stanford, CA 94305-5329., villen{at}cmgm.stanford.edu (E-mail)

Communicating editor: R. K. HERMAN

Crossing over and chiasma formation during Caenorhabditis elegans meiosis require msh-5, which encodes a conserved germline-specific MutS family member. msh-5 mutant oocytes lack chiasmata between homologous chromosomes, and crossover frequencies are severely reduced in both oocyte and spermatocyte meiosis. Artificially induced DNA breaks do not bypass the requirement for msh-5, suggesting that msh-5 functions after the initiation step of meiotic recombination. msh-5 mutants are apparently competent to repair breaks induced during meiosis, but accomplish repair in a way that does not lead to crossovers between homologs. These results combine with data from budding yeast to establish a conserved role for Msh5 proteins in promoting the crossover outcome of meiotic recombination events. Apart from the crossover deficit, progression through meiotic prophase is largely unperturbed in msh-5 mutants. Homologous chromosomes are fully aligned at the pachytene stage, and germ cells survive to complete meiosis and gametogenesis with high efficiency. Our demonstration that artificially induced breaks generate crossovers and chiasmata using the normal meiotic recombination machinery suggests (1) that association of breaks with a preinitiation complex is not a prerequisite for entering the meiotic recombination pathway and (2) that the decision for a subset of recombination events to become crossovers is made after the initiation step.

This article has been cited by other articles:

				S. Wang, M. Tang, B. Pei, X. Xiao, J. Wang, H. Hang, and L. Wu Cadmium-Induced Germline Apoptosis in Caenorhabditis elegans: The Roles of HUS1, p53, and MAPK Signaling Pathways Toxicol. Sci., April 1, 2008; 102(2): 345 - 351. [Abstract] [Full Text] [PDF]

				T. Snowden, K.-S. Shim, C. Schmutte, S. Acharya, and R. Fishel hMSH4-hMSH5 Adenosine Nucleotide Processing and Interactions with Homologous Recombination Machinery J. Biol. Chem., January 4, 2008; 283(1): 145 - 154. [Abstract] [Full Text] [PDF]

				B. Mandon-Pepin, P. Touraine, F. Kuttenn, C. Derbois, A. Rouxel, F. Matsuda, A. Nicolas, C. Cotinot, and M. Fellous Genetic investigation of four meiotic genes in women with premature ovarian failure Eur. J. Endocrinol., January 1, 2008; 158(1): 107 - 115. [Abstract] [Full Text] [PDF]

				S. Smolikov, A. Eizinger, K. Schild-Prufert, A. Hurlburt, K. McDonald, J. Engebrecht, A. M. Villeneuve, and M. P. Colaiacovo SYP-3 Restricts Synaptonemal Complex Assembly to Bridge Paired Chromosome Axes During Meiosis in Caenorhabditis elegans Genetics, August 1, 2007; 176(4): 2015 - 2025. [Abstract] [Full Text] [PDF]

				S. Smolikov, A. Eizinger, A. Hurlburt, E. Rogers, A. M. Villeneuve, and M. P. Colaiacovo Synapsis-Defective Mutants Reveal a Correlation Between Chromosome Conformation and the Mode of Double-Strand Break Repair During Caenorhabditis elegans Meiosis Genetics, August 1, 2007; 176(4): 2027 - 2033. [Abstract] [Full Text] [PDF]

				H. Feitsma, M. C. Leal, P. B. Moens, E. Cuppen, and R. W. Schulz Mlh1 Deficiency in Zebrafish Results in Male Sterility and Aneuploid as Well as Triploid Progeny in Females Genetics, April 1, 2007; 175(4): 1561 - 1569. [Abstract] [Full Text] [PDF]

				P. E. Cohen, S. E. Pollack, and J. W. Pollard Genetic Analysis of Chromosome Pairing, Recombination, and Cell Cycle Control during First Meiotic Prophase in Mammals Endocr. Rev., June 1, 2006; 27(4): 398 - 426. [Abstract] [Full Text] [PDF]

				E. Martinez-Perez and A. M. Villeneuve HTP-1-dependent constraints coordinate homolog pairing and synapsis and promote chiasma formation during C. elegans meiosis Genes & Dev., November 15, 2005; 19(22): 2727 - 2743. [Abstract] [Full Text] [PDF]

				F. Couteau and M. Zetka HTP-1 coordinates synaptonemal complex assembly with homolog alignment during meiosis in C. elegans Genes & Dev., November 15, 2005; 19(22): 2744 - 2756. [Abstract] [Full Text] [PDF]

				K. Nabeshima, A. M. Villeneuve, and M. P. Colaiacovo Crossing over is coupled to late meiotic prophase bivalent differentiation through asymmetric disassembly of the SC J. Cell Biol., February 28, 2005; 168(5): 683 - 689. [Abstract] [Full Text] [PDF]

				M. Di Giacomo, M. Barchi, F. Baudat, W. Edelmann, S. Keeney, and M. Jasin Distinct DNA-damage-dependent and -independent responses drive the loss of oocytes in recombination-defective mouse mutants PNAS, January 18, 2005; 102(3): 737 - 742. [Abstract] [Full Text] [PDF]

				J. L. Argueso, J. Wanat, Z. Gemici, and E. Alani Competing Crossover Pathways Act During Meiosis in Saccharomyces cerevisiae Genetics, December 1, 2004; 168(4): 1805 - 1816. [Abstract] [Full Text] [PDF]

				V. Jantsch, P. Pasierbek, M. M. Mueller, D. Schweizer, M. Jantsch, and J. Loidl Targeted Gene Knockout Reveals a Role in Meiotic Recombination for ZHP-3, a Zip3-Related Protein in Caenorhabditis elegans Mol. Cell. Biol., September 15, 2004; 24(18): 7998 - 8006. [Abstract] [Full Text] [PDF]

				F. W. Stahl, H. M. Foss, L. S. Young, R. H. Borts, M. F. F. Abdullah, and G. P. Copenhaver Does Crossover Interference Count in Saccharomyces cerevisiae? Genetics, September 1, 2004; 168(1): 35 - 48. [Abstract] [Full Text] [PDF]

				C. Wicky, A. Alpi, M. Passannante, A. Rose, A. Gartner, and F. Muller Multiple Genetic Pathways Involving the Caenorhabditis elegans Bloom's Syndrome Genes him-6, rad-51, and top-3 Are Needed To Maintain Genome Stability in the Germ Line Mol. Cell. Biol., June 1, 2004; 24(11): 5016 - 5027. [Abstract] [Full Text] [PDF]

				N. M. Hollingsworth and S. J. Brill The Mus81 solution to resolution: generating meiotic crossovers without Holliday junctions Genes & Dev., January 15, 2004; 18(2): 117 - 125. [Full Text] [PDF]

				T. de los Santos, N. Hunter, C. Lee, B. Larkin, J. Loidl, and N. M. Hollingsworth The Mus81/Mms4 Endonuclease Acts Independently of Double-Holliday Junction Resolution to Promote a Distinct Subset of Crossovers During Meiosis in Budding Yeast Genetics, May 1, 2003; 164(1): 81 - 94. [Abstract] [Full Text] [PDF]

				C. Her, X. Wu, M. D. Griswold, and F. Zhou Human MutS Homologue MSH4 Physically Interacts with von Hippel-Lindau Tumor Suppressor-binding Protein 1 Cancer Res., February 15, 2003; 63(4): 865 - 872. [Abstract] [Full Text] [PDF]

				A. J. MacQueen, M. P. Colaiacovo, K. McDonald, and A. M. Villeneuve Synapsis-dependent and -independent mechanisms stabilize homolog pairing during meiotic prophase in C. elegans Genes & Dev., September 15, 2002; 16(18): 2428 - 2442. [Abstract] [Full Text] [PDF]

				M. P. Colaiacovo, G. M. Stanfield, K. C. Reddy, V. Reinke, S. K. Kim, and A. M. Villeneuve A Targeted RNAi Screen for Genes Involved in Chromosome Morphogenesis and Nuclear Organization in the Caenorhabditis elegans Germline Genetics, September 1, 2002; 162(1): 113 - 128. [Abstract] [Full Text] [PDF]

				C. Rinaldo, P. Bazzicalupo, S. Ederle, M. Hilliard, and A. La Volpe Roles for Caenorhabditis elegans rad-51 in Meiosis and in Resistance to Ionizing Radiation During Development Genetics, February 1, 2002; 160(2): 471 - 479. [Abstract] [Full Text] [PDF]

				A. J. MacQueen and A. M. Villeneuve Nuclear reorganization and homologous chromosome pairing during meiotic prophase require C. elegans chk-2 Genes & Dev., July 1, 2001; 15(13): 1674 - 1687. [Abstract] [Full Text] [PDF]

				J. E. Novak, P. B. Ross-Macdonald, and G. S. Roeder The Budding Yeast Msh4 Protein Functions in Chromosome Synapsis and the Regulation of Crossover Distribution Genetics, July 1, 2001; 158(3): 1013 - 1025. [Abstract] [Full Text] [PDF]

				G. M. Chin and A. M. Villeneuve C. elegans mre-11 is required for meiotic recombination and DNA repair but is dispensable for the meiotic G2 DNA damage checkpoint Genes & Dev., March 1, 2001; 15(5): 522 - 534. [Abstract] [Full Text]