We previously proposed a "counting model" for meiotic crossover interference, in which double-strand breaks occur independently and a fixed number of noncrossovers occur between neighboring crossovers. Whereas in some organisms (group I) this simple model alone describes the crossover distribution, in other organisms (group II) an additional assumption-that some crossovers lack interference-improves the fit. Other differences exist between the groups: Group II needs double-strand breaks and some repair functions to achieve synapsis, while repair in group I generally occurs after synapsis is achieved; group II, but not group I, has recombination proteins Dmc1, Mnd1, and Hop2. Here we report experiments in msh4 mutants that are designed to test predictions of the revised model in a group II organism. Further, we interpret these experiments, the above-mentioned differences between group I and II meiosis, and other data to yield the following proposal: Group II organisms use the repair of leptotene breaks to promote synapsis by generating double-Holliday-junction intermediates that lock homologs together (pairing pathway). The possible crossover or noncrossover resolution products of these structures lack interference. In contrast, for both group I and group II, repair during pachytene (disjunction pathway) is associated with interference and generates only two resolution types, whose structures suggest that the Holliday junctions of the repair intermediates are unligated. A crossover arises when such an intermediate is stabilized by a protein that prevents its default resolution to a noncrossover. The protein-binding pattern required for interference depends on clustering of sites that have received, or are normally about to receive, meiotic double-strand breaks.A key feature of meiosis in most organisms is crossing map) and still beguiles geneticists, microscopists, and mathematicians alike. over, the process in which homologous chromosomes exchange segments during the repair of programmed A mathematical model that effectively describes linkage data from the X chromosome of Drosophila (McPeek and double-strand breaks (DSBs) in their DNA. The frequencies of crossing over provide the basis for genetic Speed 1995; Zhao et al. 1995) was put forth by Cobbs (1978) and Stam (1979). Their model, notable for its linkage mapping (Sturtevant 1913), in which the dissimplicity and mathematical tractability, was foreshadtance between genes (in morgans) is defined as the owed by several others (reviewed in Bailey 1961). It average number of points of crossing over in the interval describes the probability distribution for the linkage that separates the genes (Haldane 1919). Sturtevant distances (in morgans) between adjacent crossovers as (1915) and Muller (1916) noted that crossovers occura scaled chi-square probability distribution with an even ring during Drosophila melanogaster oogenesis show a kind number of degrees of freedom. Such a distribution of territoriality-a relatively equitable, nonrandom disgained biolog...
Using small palindromes to monitor meiotic double-strand-break-repair (DSBr) events, we demonstrate that two distinct classes of crossovers occur during meiosis in wild-type yeast. We found that crossovers accompanying 5:3 segregation of a palindrome show no conventional (i.e., positive) interference, while crossovers with 6:2 or normal 4:4 segregation for the same palindrome, in the same cross, do manifest interference. Our observations support the concept of a ''non''-interference class and an interference class of meiotic double-strand-break-repair events, each with its own rules for mismatch repair of heteroduplexes. We further show that deletion of MSH4 reduces crossover tetrads with 6:2 or normal 4:4 segregation more than it does those with 5:3 segregation, consistent with Msh4p specifically promoting formation of crossovers in the interference class. Additionally, we present evidence that an ndj1 mutation causes a shift of noncrossovers to crossovers specifically within the ''non''-interference class of DSBr events. We use these and other data in support of a model in which meiotic recombination occurs in two phases-one specializing in homolog pairing, the other in disjunction-and each producing both noncrossovers and crossovers. I N yeast, deletion of the meiosis-specific gene MSH4, which, despite its name, is said to have no involvement in mismatch repair (Ross-Macdonald and Roeder 1994), usually leaves residual crossovers, and these crossovers have reduced interference (Novak et al. 2001). In Caenorhabditis elegans, however, which is characterized by strong crossover interference as well as by cis-acting ''pairing centers'' that promote synapsis of homologous chromosomes (Dernburg et al. 1998;MacQueen et al. 2005;Phillips and Dernburg 2006), deletion of him-14, a homolog of MSH4, eliminates essentially all crossing over while apparently leaving intact the ability to repair meiotic double-strand breaks (Zalevsky et al. 1999). On the basis of these data, Zalevsky et al. (1999) suggested that yeast, and other creatures lacking pairing centers, have two kinds of crossing over, one of which is Msh4 independent, has little or no crossover interference, and serves to establish effective pairing of homologous chromosomes. Stahl et al. (2004) noted that the concept of two kinds of crossing over provides an explanation for the apparent correlation between the strength of interference and the fraction of crossovers that are Msh4 dependent in a given interval. Furthermore, Malkova et al. (2004), using a statistical analysis, which in the light of information presented here appears oversimplified, reported that the distribution of crossovers along the left arm of chromosome VII in wild-type yeast was better described by a two-kinds-of-crossover model than by the simple ''counting model'' for interference (Foss et al. 1993). More compelling support came from the phenotype of mms4 and mus81 deletions. Each of these mutations caused a reduction in crossing over but not in interference, while deletion of MMS4 a...
We have resolved a previously unidentified factor (TFIIID) that is required for in vitro transcription of polymerase III templates. Our ability to resolve factor D from each of the other components of the transcription machinery (polymerase and transcription factors IIIB and IIIC) allowed us to test the capacity of these separated components to form stable complexes with tRNA genes. We find that none of the individual components binds detectably to tRNA genes, but that certain combinations of transcription factors do bind. Our results show that TFIIID is essential for binding and that formation of a full transcription complex can proceed by either of two different pathways.
In addition to providing positional information, localization of the required region of the tRNAea gene might also allow us to recognize the particular oligonucleotides that act as transcriptional control elements. Comparison with similar regions adjacent to other Bombyx RNA polymerase III templates could reveal sequence homologies. The distribution of such conserved sequences among different classes of genes would suggest how general their control function might be.To learn whether the activity of Bombyx tRNA"Ia genes is controlled entirely by upstream elements, or whether intragenic elements are involved as well, we also examined the properties of genes from which variable amounts of coding sequence had been removed. In this paper we show that an essential upstream control region is located within the 34-nucleotide sequence immediately adjacent to the transcription initiation site. In addition, a region downstream from this site, within the 5' half of the coding region, is important for activity. We believe that certain sequences within these regions are particularly significant because they are found in other genes transcribed by Bombyx RNA polymerase III.
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