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Ajimura, M., Leem, S. H. & Ogawa, H. Identification of new genes required for meiotic recombination in Saccharomyces cerevisiae. Genetics 133, 51-66

Department of Biology, Faculty of Science, Osaka University, Japan.
Genetics (Impact Factor: 5.96). 02/1993; 133(1):51-66.
Source: PubMed

ABSTRACT

Mutants defective in meiotic recombination were isolated from a disomic haploid strain of Saccharomyces cerevisiae by examining recombination within the leu2 and his4 heteroalleles located on chromosome III. The mutants were classified into two new complementation groups (MRE2 and MRE11) and eight previously identified groups, which include SPO11, HOP1, REC114, MRE4/MEK1 and genes in the RAD52 epistasis group. All of the mutants, in which the mutations in the new complementation groups are homozygous and diploid, can undergo premeiotic DNA synthesis and produce spores. The spores are, however, not viable. The mre2 and mre11 mutants produce viable spores in a spo13 background, in which meiosis I is bypassed, suggesting that these mutants are blocked at an early step in meiotic recombination. The mre2 mutant does not exhibit any unusual phenotype during mitosis and it is, thus, considered to have a mutation in a meiosis-specific gene. By contrast, the mre11 mutant is sensitive to damage to DNA by methyl methanesulfonate and exhibits a hyperrecombination phenotype in mitosis. Among six alleles of HOP1 that were isolated, an unusual pattern of intragenic complementation was observed.

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    • "Originally, Mre11 was identified in yeast, S. cerevisiae as a gene required for early steps of meiotic recombination, namely for induction as well as for repair of meiotic DSBs. Mutational analysis of the yeast MRE11 gene showed that its function in DSB initiation is located in the C-terminal part of the protein and is distinct from its end processing function which is associated with the N-terminal part of the protein [20,25,26]. Elucidating Mre11 function in vertebrates is hampered by the fact that null mutations in any component of the MRX complex cause embryonic lethality [27-29]. "
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    ABSTRACT: The evolutionary conserved Mre11/Rad50/Nbs1 complex functions as one of the guardians of genome integrity in eukaryotes; it is required for the double-strand break repair, meiosis, DNA checkpoint, and telomere maintenance. To better understand the role of the MRE11 gene in Arabidopsis, we performed comparative analysis of several mre11 alleles with respect to genome stability and meiosis. The mre11-4 and mre11-2 alleles presumably produce truncated MRE11 proteins composed of the first 499 and 529 amino acids, respectively. Although the putative MRE11 truncated proteins differ only by 30 amino acids, the mutants exhibited strikingly different phenotypes in regards to growth morphology, genome stability and meiosis. While the mre11-2 mutants are fully fertile and undergo normal meiosis, the mre11-4 plants are sterile due to aberrant repair of meiotic DNA breaks. Structural homology analysis suggests that the T-DNA insertion in the mre11-4 allele probably disrupted the putative RAD50 interaction and/or homodimerization domain, which is assumed to be preserved in mre11-2 allele. Intriguingly, introgression of the atm-2 mutant plant into the mre11-2 background renders the double mutant infertile, a phenotype not observed in either parent line. This data indicate that MRE11 partially compensates for ATM deficiency in meiosis of Arabidopsis.
    Preview · Article · Oct 2013 · PLoS ONE
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    • "However, there are mutants of the MRN(X) complex that are competent for Spo11 cleavage, but which are unable to remove the covalently bound Spo11 protein. These include alleles of Rad50 (termed rad50-S, (Cao et al. 1990)) and nuclease-deficient alleles of Mre11 (Ajimura et al. 1993; Moreau et al. 1999). Interestingly, the same phenotype is seen in null alleles of Sae2 (Keeney and Kleckner 1995; Prinz et al. 1997). "
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    ABSTRACT: 18.1 Introduction Topoisomerase II (Top2) is an important anticancer drug target. Agents such as etoposide and doxorubicin are broadly used in a wide variety of malignancies (Baldwin and Osheroff 2005; Choi et al. 2008; Dombernowsky et al. 1996; Lieu et al. 2009; Verborg et al. 2008; Walker and Nitiss 2002). Most drugs that target Top2 generate DNA damage as a direct consequence of the catalytic activity of the enzyme. All topoisomerases cleave DNA by forming a covalent complex between the enzyme and DNA, and agents that perturb the catalytic cycle have the potential to trap the enzyme and introduce DNA damage. The DNA damage caused by interfering with a topoisomerase is unique because it includes both DNA strand breaks and protein covalently bound to DNA. Agents that lead to the trapping of topoisomerases on DNA have been termed topoisomerase poisons to highlight the importance of cellular damage induced by these agents. Because topoisomerase poisons lead to cell killing largely through enzyme-mediated damage, pathways that repair this damage are critical determinants of clinical response to these agents. A major goal of this chapter is to highlight our current understanding of how DNA repair pathways affect sensitivity to Top2 poisons. It is hoped that some of these concepts will lead to new approaches for the clinical application of Top2 targeting agents. In addition to the clinical importance of Top2 targeting agents, these drugs have served as model compounds to study cellular responses to DNA damage. Unlike ionizing radiation or alkylating agents, many Top2 targeting drugs are highly specific,
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    • "Mre11, Rad50, and Xrs2, forming the MRX complex, are conserved players in DNA repair. Mre11 was isolated in a screen for mutants with a defect in meiotic recombination (Ajimura et al., 1993). Rad50 was first described by Kupiec and Simchen (1984) and found to be needed for resistance to c-irradiation and methyl methanesulphonate (MMS). "
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    ABSTRACT: Meiosis is an essential process for sexually reproducing organisms, leading to the formation of specialized generative cells. This review intends to highlight current knowledge of early events during meiosis derived from various model organisms, including plants. It will particularly focus on cis- and trans-requirements of meiotic DNA double strand break (DSB) formation, a hallmark event during meiosis and a prerequisite for recombination of genetic traits. Proteins involved in DSB formation in different organisms, emphasizing the known factors from plants, will be introduced and their functions outlined. Recent technical advances in DSB detection and meiotic recombination analysis will be reviewed, as these new tools now allow analysis of early meiotic recombination in plants with incredible accuracy. To anticipate future directions in plant meiosis research, unpublished results will be included wherever possible.
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