The Journal of Heredity 2002:93(3)
© 2002 The American Genetic Association 93:201-205
Brief Communication |
Evidence for the Lack of Mismatch-Repair Directed Antirecombination During Mouse Meiosis
From the Molecular Biology Program, University of Southern California, 835 West 37th St., Los Angeles, CA 90089-1340 (Qin and Arnheim), Department of Nutritional Science, Morgan Hall 233, University of California at Berkeley, Berkeley, CA 94720-3104 (Baker), Division of Molecular Biology, Netherlands Cancer Institute, Plesmanlaan 121, 1066 CX Amsterdam, The Netherlands (Te Riele), and Department of Medical and Molecular Genetics, L103, Oregon Health Sciences University, 3181 SW Sam Jackson Park Rd., Portland, OR 97201-3098 (Liskay).
Address correspondence to Norman Arnheim at the address above or e-mail: arnheim{at}usc.edu.
 |
Abstract |
|---|
 Top Abstract IntroductionMaterials And MethodsResultsDiscussionReferences |
|---|
Meiotic recombination was studied in DNA mismatch repair (MMR)-deficient mice using a strain carrying a Pms2 knockout mutation. Using single-sperm typing, recombination was analyzed over five intervals on four chromosomes in four Pms2 -/- animals. A total of 1936 meioses were studied and compared to 1848 meioses from three Pms2 +/+ controls. A smaller study was carried out on a single interval in each of two chromosomes in an MMR-deficient mouse homozygous for the Msh2 knockout mutation. A total of 792 meioses were examined in the Msh2 -/- and 880 meioses in the Msh2 +/+ animal. Recombination fractions were not significantly different in either of the MMR-deficient mouse strains when compared to MMR-proficient controls. Our results appear to conflict with mouse embryonic stem (ES) cell gene-targeting experiments where MMR plays a major role in determining the efficiency of homologous recombination between nonidentical sequences. A number of possibilities could explain the apparent lack of a significant effect on meiosis.
|
Introduction |
|---|
|
TopAbstractIntroductionMaterials And MethodsResultsDiscussionReferences |
|---|
The DNA mismatch repair (MMR) system in both prokaryotes and eukaryotes can correct mutations produced during DNA replication and other DNA transactions (Buermeyer et al. 1999; Jiricny 1998; Kolodner and Marsischky 1999; Modrich 1997; Umar and Kunkel 1996). Failure to correct mismatches results in increased mutation rates. MMR also functions in recombination to remove mispairs or small insertion/deletion loops generated through heteroduplex formation. Finally, some MMR proteins are required for meiotic chromosome synapsis and crossing over.
In Escherichia coli, and in both yeast mitosis and meiosis, comparison between MMR-proficient and -deficient strains has shown that normal MMR function contributes to the suppression of recombination between nonidentical DNA sequences (homeologous sequences) in proportion to the degree of divergence between the sequences (Borts et al. 2000; Harfe and Jinks-Robertson 2000; Rayssiguier et al. 1989). The precise mechanism for this effect is not known, but presumably includes the recognition of mismatches by MMR proteins. The possibility that recombination suppression by the MMR system is a factor in speciation has been considered (Matic et al. 1995; Sniegowski 1998).
A corollary to the increase in homeologous recombination seen by inactivating MMR function is that in MMR-proficient organisms, recombination should be inhibited in proportion to the degree of sequence divergence between the homeologous chromosomes. In yeast, very low levels of sequence divergence (0.02%) do not influence the frequency of reciprocal meiotic crossing over (Borts et al. 1990), but sequences differing by about 0.1% showed a 50% decrease (Borts and Haber 1987). On the contrary, Drosophila crosses showed the same meiotic recombination fraction between sequences differing by either 0.05% or 0.32% (Hilliker et al. 1991). Crossing over between two Drosophila chromosomes completely identical by descent or from two different fly strains revealed the same level of exchange (Rutherford and Carpenter 1988), although the degree of sequence divergence between strains was not known.
In crosses between different mouse inbred strains, or between different species, no profound decrease in overall recombination is found to accompany an increase in the overall sequence differences between the parents (Dietrich et al. 1994, 1996; Rhodes et al. 1998; Silver 1995). In contrast, recombination patterns along a chromosome, especially in intersubspecific or interspecific crosses, can change significantly, with some intervals increasing while others decrease, compared to crosses between inbred strains (Dietrich et al. 1994, 1996; Heine et al. 1998; Reeves et al. 1990, 1991; Rhodes et al. 1998). The conflicting nature of these observations makes it difficult to infer what role, if any, MMR plays in meiotic recombination between nonidentical sequences in mice.
On the contrary, homologous recombination in mouse ES cells (Abuin et al. 2000; de Wind et al. 1995; Elliott and Jasin 2001; te Riele et al. 1992) is significantly inhibited when the sequence of the targeting vector and the host cell differ by as little as approximately 0.6%. If an MMR-deficient host cell is used, targeting frequencies increase up to 50-fold. In addition to gene targeting, intrachromosomal double-strand break recombination between targets also increased 10-fold when MMR-deficient cell lines were compared to wild type. A review of human gene targeting experiments suggested that isogenic DNA is not required for high frequencies of homologous recombination (Sedivy et al. 1999). However, recombination between specific sequence substrates that are 15% divergent is more efficient in MMR-deficient than in MMR-proficient human cell lines by a factor of two to three (Villemure and Belmaaza 1999).
On average, homologous chromosomes in inbred mouse strains differ from one another by a single nucleotide polymorphism approximately once every 1000 bp (0.1%; Lindblad-Toh et al. 2000). To more directly examine the extent to which the MMR system may influence meiotic crossing over in mice, we examined whether recombination in MMR-deficient individuals was increased relative to MMR-proficient animals.
|
Materials And Methods |
|---|
|
TopAbstractIntroductionMaterials And MethodsResultsDiscussionReferences |
|---|
Mouse Strains
Pms2 +/- mice with a mixed genetic background (C57BL/6J and 129 derived from the D3 embryonic stem cell line) were mated to F1 mice from a cross between BALB/cByJ and DBA/2J (CByD2F1/J; purchased from The Jackson Laboratory, Bar Harbor, ME). The Pms2 +/- offspring were intercrossed once to generate Pms2 -/- and control Pms2 +/+ males for sperm typing. The animals chosen for the recombination study were heterozygous for alleles that differed by a minimum of five CA repeats (10 base pairs) at each locus. In this way, microsatellite instability in the Pms2 -/- (or Msh2 -/-) germlines would not confuse the results, since only 0.6% of sperm have a new mutation that changes the allele size by more than two repeats (Yao et al. 1999; and our unpublished data).
Single-Sperm Typing
Using methods previously described (Baker et al. 1995; Hubert et al. 1992; Leeflang et al. 1994; Li et al. 1988), sperm suspensions were isolated from the epididymis, stained, individual sperm sorted using fluorescence-activated cell sorter, lysed and neutralized. Two rounds of polymerase chain reaction (PCR) were carried out on each sperm. In the first round, primer pairs for two different (CA)n microsatellite markers were used to amplify both loci in each sperm. A 2 µl PCR aliquot of first-round product was used in each of two separate second-round reactions; one PCR primer pair for each reaction. The primers used in the first and second rounds of PCR are given in Table 1. The sizes of the PCR products in strains that cannot be obtained from the Whitehead Institute database (http://carbon.wi.mit.edu:8000/cgi-bin/mouse/index) are shown in Table 2.
|
|
The first round of PCR consists of an initial denaturation at 94°C for 4 min, 30 cycles at 94°C for 45 s for denaturation, and one temperature for annealing and extension for 3 min, with the final extension at 72°C for 5 min. The annealing and extension temperature was 57°C for all of the markers except for D17Mit46, D17Mit66, D7Mit268, and D7Mit353. For the first two markers, annealing and extension was at 58°C and for the second two markers, 60°C. All PCRs contained 10 mM Tris-Cl (pH 8.3), 50 mM KCl, 1.5 mM MgCl2, 0.01% gelatin, 50 µM each of dATP, dGTP, dCTP, and TTP, 0.2 µM of each primer and one unit of Taq DNA polymerase in 50 µl.
The conditions for the second round were the same as for the first round except that a 90 s annealing and extension time was used. The products were resolved on 6% polyacrylamide gels, stained with ethidium bromide, and photographed under ultraviolet (UV) illumination. Analysis of a large number of sperm makes it possible to determine whether any individual sperm is a recombinant or a nonrecombinant, even if the phase is not known; for linked loci, nonrecombinant sperm are more frequent than recombinant sperm. Calculating the recombination fraction by the ratio of recombinant sperm to total sperm is subject to error. Instead, the sperm-typing data were analyzed using the TWOLOC program (Cui et al. 1989), which estimates the recombination fraction and its standard error while allowing for experimental errors: inefficient PCR, more than one sperm present in a sample, and contamination. The original sperm-typing data are available at http://www.usc.edu/dept/LAS/biosci/faculty/arnheim/.
|
Results |
|---|
|
TopAbstractIntroductionMaterials And MethodsResultsDiscussionReferences |
|---|
The breeding history of our mice could have resulted in some animals having particular chromosomal intervals homozygous for sequences from the same inbred strain or heterozygous for sequences from any of the four original strains (129 D3 embryonic stem cell line, BALB/cByJ, DBA/2J, and C57BL/6J). The latter is much more likely given that only one generation of interbreeding followed the cross between the Pms2 +/- and F1 (BALB/cByJ x DBA/2J) animals. The genotype of the markers flanking each interval in the mice chosen for sperm typing was consistent with their being heterozygous for sequences from two different inbred strains. Within any chosen interval, homologous chromosomes are estimated to differ in DNA sequence by approximately 0.1% on average (Lindblad-Toh et al. 2000). The intervals were chosen to have recombination fractions between 2.8 and 34 cM (Dietrich et al. 1996). Note that an insignificant increase in the level of sequence divergence between homologues may arise due to the elevated mutation frequency in the homozygous knockout. Using Pms2 -/- and Msh2 -/- mice containing the 84 bp SupFG1 transgene, a total mutation frequency of approximately 10-5/nucleotide was estimated in a variety of somatic cell types (Andrew et al. 2000). Extrapolating to meiotic cells, only 1% of the sequence variation over a region is expected to result from de novo mutation (10-5/10-3).
Analysis of Pms2
The genotype of the markers flanking any particular interval in both Pms2 -/- and control Pms2 +/+ animals was identical except for the D7Mit268–D7Mit353 interval. For this segment, the Pms2 -/- and control Pms2 +/+ animal had different flanking marker genotypes, but both represented heterozygosity for sequences from two different inbred strains. Recombination fractions over five intervals on four chromosomes (2, 5, 7, and 17) were determined. Sperm from some mice were analyzed in more than one interval; four different Pms2 -/- and three different Pms2 +/+ animals were used (Table 3). Table 3 summarizes the recombination fractions and 95% confidence intervals (CIs) derived using the TWOLOC program for the chosen intervals. For each interval, there was an overlap between the 95% CIs. Thus no significant increase was detected in the recombination fraction in sperm from MMR-deficient compared to MMR-proficient animals. Power calculations (Table 3 and legend) show that the sample size of sperm we studied would have allowed us to detect a minimum of a 1.4- to 2.3-fold increase (depending on the interval) in recombination in Pms2 -/- compared to Pms2 +/+ mice with 95% certainty.
|
Analysis of Msh2
One Msh2 +/+ and one Msh2 -/- mouse of mixed genetic origin (129/Ola and FVB; F3 offspring from a cross between 129/Ola Msh2 +/- and FVB Msh2 +/+) was also studied (de Wind et al. 1995). In both animals the two intervals were heterozygous for sequences from 129/Ola on one homologue and FVB on the other homologue. The sperm recombination fractions are shown in Table 3. Again, no significant increase could be detected in the Msh2 -/- mouse compared to the wild-type control. Power calculations (Table 3 and legend) indicated a 95% certainty of detecting a minimum of a 1.6- to 2.1-fold increase in recombination in the Msh2 -/- animals (depending on the specific interval).
|
Discussion |
|---|
|
TopAbstractIntroductionMaterials And MethodsResultsDiscussionReferences |
|---|
A total of 74 cM of genetic distance was studied for the effects of Pms2 deficiency on recombination. Only 6.7 cM (the intervals on chromosome 2) were not chosen randomly, but had been identified as being in a "cold spot" for mouse recombination (Nachman and Churchill 1996; Nachman MW, personal communication). One possible explanation for a cold spot is that the region has a very high level of polymorphism that might reduce recombination in MMR-proficient animals.
Two MMR genes, Pms2 and Msh2, were chosen for study. Pms2 -/- females are fertile, but the males are sterile (Baker et al. 1995). The sperm number in Pms2 -/- males is approximately 25% that of a +/+ animal. Cytological studies have shown that approximately 20% of the Pms2 -/- male meiotic prophase cells have normally synapsed chromosomes (Baker et al. 1995). Given the similarity between these two percentages, it is likely that the sperm we isolated had completed a normal meiosis. Both male and female Msh2 -/- animals are fertile (de Wind et al. 1995). Note that mice homozygous for a knockout of the Mlh1 MMR gene are deficient in MMR function and are sterile in both males and females due to a block in meiotic diplotene associated with prematurely separated chromosomes and consistent with reduced recombination (Baker et al. 1996; Edelmann et al. 1996; Woods et al. 1999). In MMR-proficient mice, the position and number of foci with Mlh1 protein correlates strongly with the distribution and chiasma number seen on diplotene chromosomes at metaphase I (Anderson et al. 1999).
The previously cited data on MMR-directed antirecombination in E. coli, yeast mitosis and meiosis, and on gene targeting experiments in mouse ES cells raised the possibility that MMR deficiency might also increase meiotic recombination between mouse chromosome intervals differing in DNA sequence compared to MMR-proficient animals. Consistent with this idea are recent data showing that mitotic recombination frequencies at the Aprt locus is suppressed in F1 animals derived from interspecific and intersubspecific crosses when compared to animals from crosses between inbred strains (Shao et al. 2001).
However, the results on sperm from mice lacking Pms2 gene function show little effect on meiotic crossing over within the approximately 148 Mb of DNA that was examined (74 cM x 2 Mb/cM). Because of the complex genetic backgrounds of the individual mice we examined, the exact degree of sequence similarity between homologues in any of the specific intervals we examined is not known. However, there is no reason to believe that, in most of the studied intervals, the homologues differed from one another less than the genome average of 0.1% observed between inbred strains (Lindblad-Toh et al. 2000). Although only 18.4 cM (approximately 36.8 Mb) were studied in the experiment on Msh2, a similar conclusion is suggested. Note that the recombination fraction for the D2Mit58–D2Mit126 interval in the Msh2 +/+ and -/- mice was not significantly different from that seen in the Pms2 crosses, even though the mice had entirely different genetic backgrounds.
It is not known whether meiotic crossing over between interspersed repeated sequences that differ from each other by more than 0.1% can occur in MMR-deficient mice. However, the normal fertility of both male and female Msh2 -/- mice (de Wind et al. 1995; Reitmair et al. 1995) and Pms2 -/- females (Baker et al. 1995) does not suggest a very large increase in recombination between homeologous sequences in an MMR-deficient background. The sterility of Pms2 -/- males is unlikely to result from an increase in homeologous recombination, since analysis of meiotic cells did not reveal synaptic configurations typical of intra- or interchromosomal exchanges, but instead showed disruptions of meiotic prophase I, primarily chromosome asynapsis (Baker et al. 1995). It is known that both the Pms2 and Msh2 genes are normally expressed in spermatogonia and at the early stages of meiotic prophase (Richardson et al. 2000).
All sperm from Pms2 -/- males have misshapen heads and severely truncated tails (Baker et al. 1995). This abnormal morphology may result from the abnormally synapsed prophase cells initiating a meiotic checkpoint pathway. The onset of apoptosis (Odorisio et al. 1998) may lead to abnormal sperm morphology of even the prophase cells that had undergone normal synapsis and recombination, since both cell types differentiate in the same syncytium.
Our results do not prove that in MMR-proficient mice meiotic recombination between 100% identical sequences and homologues that differed by 0.1% on average would be the same. A 0.1% level of sequence difference might affect meiotic crossing over locally, as predicted from the ES cell gene targeting assays. A direct demonstration of this would require the development of specific assays that can detect the very low meiotic recombination fractions between homologous chromosomes expected over very small DNA intervals. Such assays have been used to study rare human meiotic recombination events (Buard et al. 2000; Han et al. 2000; Tusie-Luna and White 1995). Alternatively, model systems using test sequences to measure intrachromosomal or interchromosomal recombination in mouse meiosis could also be examined (Cooper et al. 1998; Moynahan et al. 1996).
Even if local recombination is reduced by a low level of mismatches, several possibilities could explain why this might not lead to an observed reduction in crossing over at the megabase resolution we examined by single-sperm typing. First, mouse meiotic crossing over events, including initiation, branch migration, and resolution, could take place in DNA segments shorter than the average distance (approximately 1000 bp; Lindblad-Toh et al. 2000) between polymorphic sites. Given this density of polymorphisms, statistical considerations predict that some regions in a particular multimegabase interval contain a higher, and some a lower, density of polymorphic sites than the average for the whole interval. In the low-density intervals there would be little likelihood that a mismatch would be encountered in the 1000 bp window, and therefore crossing over would be the same in wild-type and MMR-deficient strains. Alternatively, inhibition of crossing over by a mismatch in one region may result in the reinitiation of crossing over in an adjacent region where, by chance alone, mismatches will be less likely. Finally, the initiation of crossing over might occur preferentially in regions with identical sequences on both homologues. Under each of these models, the presence or absence of MMR function would have little, if any, effect on meiotic crossing over in relatively large intervals between homologous chromosomes.
How can the sensitivity to mismatches seen in mouse ES cell gene targeting and intrachromosomal recombination assays (Abuin et al. 2000; de Wind et al. 1995; Elliott and Jasin 2001; te Riele et al. 1992) be reconciled with our results on meiotic crossing over? Studies on somatic cells in culture may not reflect what goes on in meiotic cells in the animal. The effect of mismatches on somatic cell recombination may be based on a mechanism that evolved to reduce the chromosomal integration of small DNA fragments that might arise in a cell during normal metabolism. During meiosis this mechanism may be suppressed to allow nonidentical homologues to undergo crossing over and permit proper chromosome segregation. Additional mechanisms (Goldman and Lichten 2000) may be primarily responsible for limiting meiotic recombination between interspersed repeated sequences on the same or different chromosomes.
|
Footnotes |
|---|
Corresponding Editor: Muriel Davisson
Received February 11, 2002
Accepted March 5, 2002
|
References |
|---|
|
TopAbstractIntroductionMaterials And MethodsResultsDiscussionReferences |
|---|
-
Abuin A, Zhang H, and Bradley A, 2000. Genetic analysis of mouse embryonic stem cells bearing Msh3 and Msh2 single and compound mutations. Mol Cell Biol 20:149–157.
Anderson LK, Reeves A, Webb LM, and Ashley T, 1999. Distribution of crossing over on mouse synaptonemal complexes using immunofluorescent localization of MLH1 protein. Genetics 151:1569–1579.
Andrew SE, Xu XS, Baross-Francis A, Narayanan L, Milhausen K, Liskay RM, Jirik FR, and Glazer PM, 2000. Mutagenesis in PMS2- and MSH2-deficient mice indicates differential protection from transversions and frameshifts. Carcinogenesis 21:1291–1295.
Baker SM, Bronner CE, Zhang L, Plug AW, Robatzek M, Warren G, Elliott EA, Yu J, Ashley T, Arnheim N, Flavell RA, and Liskay RM, 1995. Male mice defective in the DNA mismatch repair gene PMS2 exhibit abnormal chromosome synapsis in meiosis. Cell 82:309–319.[CrossRef][ISI][Medline]
Baker SM, Plug AW, Prolla TA, Bronner CE, Harris AC, Yao X, Christie DM, Monell C, Arnheim N, Bradley A, Ashley T, and Liskay RM, 1996. Involvement of mouse Mlh1 in DNA mismatch repair and meiotic crossing over [see comments]. Nat Genet 13:336–342.[CrossRef][ISI][Medline]
Blake JA, Eppig JT, Richardson JE, and Davisson MT, 2000. The Mouse Genome Database (MGD): expanding genetic and genomic resources for the laboratory mouse. The Mouse Genome Database Group. Nucleic Acids Res 28:108–111.
Borts RH, Chambers SR, and Abdullah MF, 2000. The many faces of mismatch repair in meiosis. Mutat Res 451:129–150.[ISI][Medline]
Borts RH and Haber JE, 1987. Meiotic recombination in yeast: alteration by multiple heterozygosities. Science 237:1459–1465.
Borts RH, Leung WY, Kramer W, Kramer B, Williamson M, Fogel S, and Haber JE, 1990. Mismatch repair-induced meiotic recombination requires the pms1 gene product. Genetics 124:573–584.[Abstract]
Buard J, Shone AC, and Jeffreys AJ, 2000. Meiotic recombination and flanking marker exchange at the highly unstable human minisatellite CEB1 (D2S90). Am J Hum Genet 67:333–344.[CrossRef][ISI][Medline]
Buermeyer AB, Deschenes SM, Baker SM, and Liskay RM, 1999. Mammalian DNA mismatch repair. Annu Rev Genet 33:533–564.[CrossRef][ISI][Medline]
Cooper DM, Schimenti KJ, and Schimenti JC, 1998. Factors affecting ectopic gene conversion in mice. Mamm Genome 9:355–360.[CrossRef][ISI][Medline]
Cui XF, Li HH, Goradia TM, Lange K, Kazazian HH Jr, Galas D, and Arnheim N, 1989. Single-sperm typing: determination of genetic distance between the G gamma-globin and parathyroid hormone loci by using the polymerase chain reaction and allele-specific oligomers. Proc Natl Acad Sci USA 86:9389–9393.
de Wind N, Dekker M, Berns A, Radman M, and te Riele H, 1995. Inactivation of the mouse Msh2 gene results in mismatch repair deficiency, methylation tolerance, hyperrecombination, and predisposition to cancer. Cell 82:321–330.[CrossRef][ISI][Medline]
Dietrich WF, Miller J, Steen R, Merchant MA, Damron-Boles D, Husain Z, Dredge R, Daly MJ, Ingalls KA, O'Connor TJ, Evans CA, DeAngelis MM, Levinson DM, Kruglyak L, Goodman N, Copeland NG, Jenkins NA, Hawkins TL, Stein L, Page DC, and Lander ES, 1996. A comprehensive genetic map of the mouse genome [see comments] [published erratum appears in Nature 1996;381(6578):172]. Nature 380:149–152.[CrossRef][Medline]
Dietrich WF, Miller JC, Steen RG, Merchant M, Damron D, Nahf R, Gross A, Joyce DC, Wessel M, Dredge RD, Marquis A, Stein LD, Goodman N, Page DC, and Lander ES, 1994. A genetic map of the mouse with 4,006 simple sequence length polymorphisms [see comments]. Nat Genet 7:220–245.[CrossRef][ISI][Medline]
Edelmann W, Cohen PE, Kane M, Lau K, Morrow B, Bennett S, Umar A, Kunkel T, Cattoretti G, Chaganti R, Pollard JW, Kolodner RD, and Kucherlapati R, 1996. Meiotic pachytene arrest in MLH1-deficient mice. Cell 85:1125–1134.[CrossRef][ISI][Medline]
Elliott B and Jasin M, 2001. Repair of double-strand breaks by homologous recombination in mismatch repair-defective mammalian cells. Mol Cell Biol 21:2671–2682.
Goldman AS and Lichten M, 2000. Restriction of ectopic recombination by interhomolog interactions during Saccharomyces cerevisiae meiosis. Proc Natl Acad Sci USA 97:9537–9542.
Han LL, Keller MP, Navidi W, Chance PF, and Arnheim N, 2000. Unequal exchange at the Charcot-Marie-Tooth disease type 1A recombination hot-spot is not elevated above the genome average rate [in process citation]. Hum Mol Genet 9:1881–1889.
Harfe BD and Jinks-Robertson S, 2000. Mismatch repair proteins and mitotic genome stability. Mutat Res 451:151–167.[ISI][Medline]
Heine D, Khambata S, and Passmore HC, 1998. High-resolution mapping and recombination interval analysis of mouse chromosome 17. Mamm Genome 9:511–516.[CrossRef]
Hilliker AJ, Clark SH, and Chovnick A, 1991. The effect of DNA sequence polymorphisms on intragenic recombination in the rosy locus of Drosophila melanogaster. Genetics 129:779–781.[Abstract]
Hubert R, Weber JL, Schmitt K, Zhang L, and Arnheim N, 1992. A new source of polymorphic DNA markers for sperm typing: analysis of microsatellite repeats in single cells. Am J Hum Genet 51:985–991.[ISI][Medline]
Jiricny J, 1998. Eukaryotic mismatch repair: an update. Mutat Res 409:107–121.[ISI][Medline]
Kolodner RD and Marsischky GT, 1999. Eukaryotic DNA mismatch repair. Curr Opin Genet Dev 9:89–96.[CrossRef][ISI][Medline]
Leeflang EP, Hubert R, Schmitt K, Zhang L, and Arnheim N, 1994. Single sperm typing. Curr Protocols Hum Genet 1:1.6.1–1.6.15.
Li HH, Gyllensten UB, Cui XF, Saiki RK, Erlich HA, and Arnheim N, 1988. Amplification and analysis of DNA sequences in single human sperm and diploid cells. Nature 335:414–417.[CrossRef][Medline]
Lindblad-Toh K, Winchester E, Daly MJ, Wang DG, Hirschhorn JN, Laviolette JP, Ardlie K, Reich DE, Robinson E, Sklar P, Shah N, Thomas D, Fan JB, Gingeras T, Warrington J, Patil N, Hudson TJ, and Lander ES, 2000. Large-scale discovery and genotyping of single-nucleotide polymorphisms in the mouse. Nat Genet 24:381–386.[CrossRef][ISI][Medline]
Matic I, Rayssiguier C, and Radman M, 1995. Interspecies gene exchange in bacteria: the role of SOS and mismatch repair systems in evolution of species. Cell 80:507–515.[CrossRef][ISI][Medline]
Modrich P, 1997. Strand-specific mismatch repair in mammalian cells. J Biol Chem 272:24727–24730.
Moynahan ME, Akgun E, and Jasin M, 1996. A model for testing recombinogenic sequences in the mouse germline. Hum Mol Genet 5:875–886.
Nachman MW and Churchill GA, 1996. Heterogeneity in rates of recombination across the mouse genome. Genetics 142:537–548.[Abstract]
Odorisio T, Rodriguez TA, Evans EP, Clarke AR, and Burgoyne PS, 1998. The meiotic checkpoint monitoring synapsis eliminates spermatocytes via p53-independent apoptosis [see comments]. Nat Genet 18:257–261.[CrossRef][ISI][Medline]
Rayssiguier C, Thaler DS, and Radman M, 1989. The barrier to recombination between Escherichia coli and Salmonella typhimurium is disrupted in mismatch-repair mutants. Nature 342:396–401.[CrossRef][Medline]
Reeves RH, Crowley MR, Moseley WS, and Seldin MF, 1991. Comparison of interspecific to intersubspecific backcrosses demonstrates species and sex differences in recombination frequency on mouse chromosome 16. Mamm Genome 1:158–164.[CrossRef][ISI][Medline]
Reeves RH, Crowley MR, O'Hara BF, and Gearhart JD, 1990. Sex, strain, and species differences affect recombination across an evolutionarily conserved segment of mouse chromosome 16. Genomics 8:141–148.[CrossRef][ISI][Medline]
Reitmair AH, Schmits R, Ewel A, Bapat B, Redston M, Mitri A, Waterhouse P, Mittrucker HW, Wakeham A, Liu B, Thomason A, Griesser H, Gallinger S, Ballhausen WG, Fishel R, and Mak TW, 1995. MSH2 deficient mice are viable and susceptible to lymphoid tumours. Nat Genet 11:64–70.[CrossRef][ISI][Medline]
Rhodes M, Straw R, Fernando S, Evans A, Lacey T, Dearlove A, Greystrong J, Walker J, Watson P, Weston P, Kelly M, Taylor D, Gibson K, Mundy C, Bourgade F, Poirier C, Simon D, Brunialti AL, Montagutelli X, Gu'enet JL, Haynes A, and Brown SD, 1998. A high-resolution microsatellite map of the mouse genome. Genome Res 8:531–542.
Richardson LL, Pedigo C, and Handel MA, 2000. Expression of deoxyribonucleic acid repair enzymes during spermatogenesis in mice. Biol Reprod 62:789–796.
Rutherford SL and Carpenter AT, 1988. The effect of sequence homozygosity on the frequency of X-chromosomal exchange in Drosophila melanogaster females. Genetics 120:725–732.
Sedivy JM, Vogelstein B, Liber HM, Hendrickson EA, and Rosmarin A, 1999. Gene targeting in human cells without isogenic DNA. Science 283:9.
Shao C, Stambrook PJ, and Tischfield JA, 2001. Mitotic recombination is suppressed by chromosomal divergence in hybrids of distantly related mouse strains. Nat Genet 28:169–172.[CrossRef][ISI][Medline]
Silver L, 1995. Mouse Genetics. New York: Oxford University Press.
Sniegowski P, 1998. Mismatch repair: origin of species? Curr Biol 8:R59–R61.[CrossRef][ISI][Medline]
te Riele H, Maandag ER, and Berns A, 1992. Highly efficient gene targeting in embryonic stem cells through homologous recombination with isogenic DNA constructs. Proc Natl Acad Sci USA 89:5128–5132.
Tusie-Luna MT and White PC, 1995. Gene conversions and unequal crossovers between CYP21 (steroid 21-hydroxylase gene) and CYP21P involve different mechanisms. Proc Natl Acad Sci USA 92:10796–10800.
Umar A and Kunkel TA, 1996. DNA-replication fidelity, mismatch repair and genome instability in cancer cells. Eur J Biochem 238:297–307.[ISI][Medline]
Villemure JF and Belmaaza A, 1999. Effects of sequence divergence on the efficiency of extrachromosomal recombination in mismatch repair proficient and deficient mammalian cell lines. Somat Cell Mol Genet 25:79–90.[CrossRef][Medline]
Woods LM, Hodges CA, Baart E, Baker SM, Liskay M, and Hunt PA, 1999. Chromosomal influence on meiotic spindle assembly: abnormal meiosis I in female Mlh1 mutant mice. J Cell Biol 145:1395–1406.
Yao X, Buermeyer AB, Narayanan L, Tran D, Baker SM, Prolla TA, Glazer PM, Liskay RM, and Arnheim N, 1999. Different mutator phenotypes in Mlh1- versus Pms2-deficient mice. Proc Natl Acad Sci USA 96:6850–6855.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  J. Wesoly, S. Agarwal, S. Sigurdsson, W. Bussen, S. Van Komen, J. Qin, H. van Steeg, J. van Benthem, E. Wassenaar, W. M. Baarends, et al. Differential Contributions of Mammalian Rad54 Paralogs to Recombination, DNA Damage Repair, and Meiosis Mol. Cell. Biol., February 1, 2006; 26(3): 976 - 989. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. K. Kolas, A. Svetlanov, M. L. Lenzi, F. P. Macaluso, S. M. Lipkin, R. M. Liskay, J. Greally, W. Edelmann, and P. E. Cohen Localization of MMR proteins on meiotic chromosomes in mice indicates distinct functions during prophase I J. Cell Biol., November 7, 2005; 171(3): 447 - 458. [Abstract] [Full Text] [PDF]
|
|
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||