Heteroduplex DNA correction in Saccharomyces cerevisiae is mismatch specific and requires functional PMS genes.

Kramer, Barbara; Kramer, Wilfried; Williamson, Marsha S.; Fogel, Seymour

doi:10.1128/mcb.9.10.4432

Cited by 160 publications

(131 citation statements)

References 68 publications

Supporting

Mentioning

117

Contrasting

Order By: Relevance

“…There is ample precedent for poorly repaired mismatches escaping correction during meiosis in wild-type, i.e., mismatch repair proficient, fungi (for example, see refs. [26][27][28][29].…”

Section: Discussionmentioning

confidence: 99%

Meiotic crossover hotspots contained in haplotype block boundaries of the mouse genome

Kauppi

Jasin

Keeney

2007

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Fertility requires successful chromosome segregation in meiosis, which in most sexual organisms depends on the formation of appropriately placed crossovers. The nonrandom genome-wide distributions of meiotic recombination events have been examined at the molecular level experimentally in yeast and by inference from linkage disequilibrium patterns in humans. Thus far, no method has existed for pinpointing sites of crossing-over on a genome-wide scale in an experimentally tractable animal whose genome size and complexity models that of humans. Here, we present a genomic approach to identify mouse crossover hotspots, based on targeting haplotype block boundaries. This represents a previously undescribed method potentially applicable to largescale mouse hotspot identification. Using this method, we have successfully predicted the location of two previously uncharacterized crossover hotspots in male mice. As increasing amounts of single-nucleotide polymorphism data emerge, this approach will be useful for investigating the recombination landscape of the mouse genome.meiosis ͉ mouse strain ͉ recombination ͉ single-nucleotide polymorphism ͉ allele-specified PCR M uch of the human genome consists of discrete chromosomal segments within which single-nucleotide polymorphisms (SNPs) are strongly associated (1-5). These segments, known as haplotype blocks, or linkage disequilibrium (LD) blocks, are 7-to 16-kb long on average, depending on the population (5). Haplotype block structure in humans is largely generated by the presence of preferred sites (''hotspots'') for meiotic crossing-over, flanked by recombinationally inert DNA (6-9). The handful of human recombination hotspots analyzed at high resolution vary in their overall cross-over activity, but share the feature of having crossovers clustered within narrow, 1-to 2-kb regions (6, 7). High-resolution analysis of two hotspots in the mouse, initially identified from pedigree data, revealed similar properties (10, 11).Extrapolating from extensive studies in yeast, it is likely that mammalian crossover hotspots are preferred sites for formation of the DNA double-strand breaks that initiate meiotic recombination (reviewed in refs. 12-14). However, although the existence of hotspots is well documented, the molecular mechanisms that control their activity are poorly understood. Availability of an experimentally tractable mammalian system for characterizing and manipulating hotspots is thus important.Breakdown of LD, that is, disruption of haplotype block structure, reports on recombination that occurred during the history of the population. Thus, LD analysis is the current method for studying genome-wide fine-scale patterns of recombination in humans (reviewed in ref. 13). However, LD analysis is less suited for this purpose in mice, because of two features of the short and unusual population history of inbred laboratory strains. First, it has been argued that there is strong selection pressure to eliminate allelic combinations that cannot be tolerated in homozygous form (15)...

show abstract

“…There is ample precedent for poorly repaired mismatches escaping correction during meiosis in wild-type, i.e., mismatch repair proficient, fungi (for example, see refs. [26][27][28][29].…”

Section: Discussionmentioning

confidence: 99%

Meiotic crossover hotspots contained in haplotype block boundaries of the mouse genome

Kauppi

Jasin

Keeney

2007

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…The TRG1/ PDI1 gene of yeast encodes an ER-resident protein that is structurally related to PDI and essential for growth. The complementation experiments were performed in BK203-15B cells carrying a deletion of the TRG1 gene, which can be rescued by the pWBK-PDI centromeric plasmid (Kramer et al, 1989). This centromeric vector carries a URA3 gene, which allows positive selection for growth in the absence of uracil and negative selection in the presence of 5-fluoroorotic acid (5-FOA).…”

Section: Pdil2-1 Can Rescue a Pdi Null Mutant Of Yeastmentioning

confidence: 99%

Truncation of a Protein Disulfide Isomerase, PDIL2-1, Delays Embryo Sac Maturation and Disrupts Pollen Tube Guidance inArabidopsis thaliana

et al. 2008

View full text Add to dashboard Cite

Pollen tubes must navigate through different female tissues to deliver sperm to the embryo sac for fertilization. Protein disulfide isomerases play important roles in the maturation of secreted or plasma membrane proteins. Here, we show that certain T-DNA insertions in Arabidopsis thaliana PDIL2-1, a protein disulfide isomerase (PDI), have reduced seed set, due to delays in embryo sac maturation. Reciprocal crosses indicate that these mutations acted sporophytically, and aniline blue staining and scanning electron microscopy showed that funicular and micropylar pollen tube guidance were disrupted. A PDIL2-1-yellow fluorescent protein fusion was mainly localized in the endoplasmic reticulum and was expressed in all tissues examined. In ovules, expression in integument tissues was much higher in the micropylar region in later developmental stages, but there was no expression in embryo sacs. We show that reduced seed set occurred when another copy of full-length PDIL2-1 or when enzymatically active truncated versions were expressed, but not when an enzymatically inactive version was expressed, indicating that these T-DNA insertion lines are gain-of-function mutants. Our results suggest that these truncated versions of PDIL2-1 function in sporophytic tissues to affect ovule structure and impede embryo sac development, thereby disrupting pollen tube guidance.

show abstract

“…In S. cerevisiae, multiple MutS and MutL homologs have been identified, with five MutS homologs (Msh1p to Msh5p) and three MutL homologs (Pms1p, Mlh1p, and Mlh2p) having been described to date (17,22,36,43,49,52,62). Msh2p, Msh3p, Pms1p, and Mlh1p are important for correcting mismatches arising during nuclear DNA replication and recombination (21,36,43,50,62,63,70). Mutations in MSH2, PMS1, and MLH1 result in strong mutator phenotypes, increase postmeiotic segregation of heterozygous markers, and greatly destabilize simple repeats.…”

mentioning

confidence: 99%

Mitotic Crossovers between Diverged Sequences Are Regulated by Mismatch Repair Proteins in Saccharomyces cerevisiae

Datta

Adjiri

New

et al. 1996

Molecular and Cellular Biology

204

192

View full text Add to dashboard Cite

Mismatch repair systems correct replication-and recombination-associated mispaired bases and influence the stability of simple repeats. These systems thus serve multiple roles in maintaining genetic stability in eukaryotes, and human mismatch repair defects have been associated with hereditary predisposition to cancer. In prokaryotes, mismatch repair systems also have been shown to limit recombination between diverged (homeologous) sequences. We have developed a unique intron-based assay system to examine the effects of yeast mismatch repair genes (PMS1, MSH2, and MSH3) on crossovers between homeologous sequences. We find that the apparent antirecombination effects of mismatch repair proteins in mitosis are related to the degree of substrate divergence. Defects in mismatch repair can elevate homeologous recombination between 91% homologous substrates as much as 100-fold while having only modest effects on recombination between 77% homologous substrates. These observations have implications for genome stability and general mechanisms of recombination in eukaryotes.Much of our knowledge concerning the mechanism of homologous recombination in eukaryotes has come from studies done with the yeast Saccharomyces cerevisiae (for a review, see reference 40), in which two basic types of recombination occur: reciprocal recombination (crossing-over) and nonreciprocal recombination (gene conversion). Reciprocal recombination events involve the physical exchange of information between chromosomes and hence alter the genetic linkages of markers on either side of the crossover event. Gene conversion events involve the unidirectional transfer of information from one chromosome to another and are nonrandomly associated with crossing-over. The association between gene conversion and crossing-over has been central to developing molecular models of recombination in which conversion events reflect the formation of a heteroduplex intermediate that can be resolved in either a crossover or noncrossover mode (16,30,67). Homologous recombination is usually thought of as occurring between sequences at identical positions on homologous chromosomes (allelic recombination), but it also can involve similar sequences at nonallelic (ectopic) locations (for reviews, see references 20 and 39). A large number of repeated sequences are found dispersed throughout eukaryotic genomes and can serve as substrates for ectopic recombination events. Such repeats exhibit various degrees of homology at the DNA level and are referred to as being homeologous to reflect their partial homology. Ectopic gene conversion between homeologous sequences can lead to the homogenization of repeats and is likely to be an important mechanism for the concerted evolution of multigene families (12). It also can generate novel sequence combinations within a gene family and has been implicated as a possible source of diversity at immunoglobulin loci (6, 28). Crossing-over between dispersed repeats results in genome rearrangements (deletions, duplications, inversions, and translo...

show abstract

Heteroduplex DNA correction in Saccharomyces cerevisiae is mismatch specific and requires functional PMS genes.

Cited by 160 publications

References 68 publications

Meiotic crossover hotspots contained in haplotype block boundaries of the mouse genome

Meiotic crossover hotspots contained in haplotype block boundaries of the mouse genome

Truncation of a Protein Disulfide Isomerase, PDIL2-1, Delays Embryo Sac Maturation and Disrupts Pollen Tube Guidance inArabidopsis thaliana

Mitotic Crossovers between Diverged Sequences Are Regulated by Mismatch Repair Proteins in Saccharomyces cerevisiae

Contact Info

Product

Resources

About