Evidence for joint genic control of spontaneous mutation and genetic recombination during mitosis inSaccharomyces

1977 ◽  
Vol 150 (2) ◽  
pp. 127-135 ◽  
Author(s):  
John E. Golin ◽  
Michael S. Esposito
Keyword(s):  
Genetic Recombination ◽  
Spontaneous Mutation ◽  
Genic Control

Dual requirement in yeast DNA mismatch repair for MLH1 and PMS1, two homologs of the bacterial mutL gene

1994 ◽  
Vol 14 (1) ◽  
pp. 407-415
Author(s):  
T A Prolla ◽  
D M Christie ◽  
R M Liskay
Keyword(s):  
Mismatch Repair ◽  
Dna Mismatch Repair ◽  
Genetic Recombination ◽  
Sequence Similarity ◽  
Spontaneous Mutation ◽  
Protein Product ◽  
Mlh1 Gene ◽  
Dna Mismatch ◽  
Postmeiotic Segregation ◽  
Simple Sequence

We have identified a new Saccharomyces cerevisiae gene, MLH1 (mutL homolog), that encodes a predicted protein product with sequence similarity to DNA mismatch repair proteins of bacteria (MutL and HexB) and S. cerevisiae yeast (PMS1). Disruption of the MLH1 gene results in elevated spontaneous mutation rates during vegetative growth as measured by forward mutation to canavanine resistance and reversion of the hom3-10 allele. Additionally, the mlh1 delta mutant displays a dramatic increase in the instability of simple sequence repeats, i.e., (GT)n (M. Strand, T. A. Prolla, R. M. Liskay, and T. D. Petes, Nature [London] 365:274-276, 1993). Meiotic studies indicate that disruption of the MLH1 gene in diploid strains causes increased spore lethality, presumably due to the accumulation of recessive lethal mutations, and increased postmeiotic segregation at each of four loci, the latter being indicative of inefficient repair of heteroduplex DNA generated during genetic recombination. mlh1 delta mutants, which should represent the null phenotype, show the same mutator and meiotic phenotypes as isogenic pms1 delta mutants. Interestingly, mutator and meiotic phenotypes of the mlh1 delta pms1 delta double mutant are indistinguishable from those of the mlh1 delta and pms1 delta single mutants. On the basis of our data, we suggest that in contrast to Escherichia coli, there are two MutL/HexB-like proteins in S. cerevisiae and that each is a required component of the same DNA mismatch repair pathway.

scholarly journals Dual requirement in yeast DNA mismatch repair for MLH1 and PMS1, two homologs of the bacterial mutL gene.

1994 ◽  
Vol 14 (1) ◽  
pp. 407-415 ◽  
Author(s):  
T A Prolla ◽  
D M Christie ◽  
R M Liskay
Keyword(s):  
Mismatch Repair ◽  
Dna Mismatch Repair ◽  
Genetic Recombination ◽  
Sequence Similarity ◽  
Spontaneous Mutation ◽  
Protein Product ◽  
Mlh1 Gene ◽  
Dna Mismatch ◽  
Postmeiotic Segregation ◽  
Simple Sequence

We have identified a new Saccharomyces cerevisiae gene, MLH1 (mutL homolog), that encodes a predicted protein product with sequence similarity to DNA mismatch repair proteins of bacteria (MutL and HexB) and S. cerevisiae yeast (PMS1). Disruption of the MLH1 gene results in elevated spontaneous mutation rates during vegetative growth as measured by forward mutation to canavanine resistance and reversion of the hom3-10 allele. Additionally, the mlh1 delta mutant displays a dramatic increase in the instability of simple sequence repeats, i.e., (GT)n (M. Strand, T. A. Prolla, R. M. Liskay, and T. D. Petes, Nature [London] 365:274-276, 1993). Meiotic studies indicate that disruption of the MLH1 gene in diploid strains causes increased spore lethality, presumably due to the accumulation of recessive lethal mutations, and increased postmeiotic segregation at each of four loci, the latter being indicative of inefficient repair of heteroduplex DNA generated during genetic recombination. mlh1 delta mutants, which should represent the null phenotype, show the same mutator and meiotic phenotypes as isogenic pms1 delta mutants. Interestingly, mutator and meiotic phenotypes of the mlh1 delta pms1 delta double mutant are indistinguishable from those of the mlh1 delta and pms1 delta single mutants. On the basis of our data, we suggest that in contrast to Escherichia coli, there are two MutL/HexB-like proteins in S. cerevisiae and that each is a required component of the same DNA mismatch repair pathway.

scholarly journals Mutation at the Polymerase Active Site of Mouse DNA Polymerase δ Increases Genomic Instability and Accelerates Tumorigenesis

2007 ◽  
Vol 27 (21) ◽  
pp. 7669-7682 ◽  
Author(s):  
Ranga N. Venkatesan ◽  
Piper M. Treuting ◽  
Evan D. Fuller ◽  
Robert E. Goldsby ◽  
Thomas H. Norwood ◽  
...  
Keyword(s):  
Genomic Instability ◽  
Dna Polymerase ◽  
Active Site ◽  
Genetic Recombination ◽  
Human Cancer ◽  
Disease Incidence ◽  
Spontaneous Mutation ◽  
Heterozygous Mutation ◽  
Wild Type ◽  
Dna Polymerase Δ

ABSTRACT Mammalian DNA polymerase δ (Pol δ) is believed to replicate a large portion of the genome and to synthesize DNA in DNA repair and genetic recombination pathways. The effects of mutation in the polymerase domain of this essential enzyme are unknown. Here, we generated mice harboring an L604G or L604K substitution in highly conserved motif A in the polymerase active site of Pol δ. Homozygous Pold1 L604G/L604G and Pold1 L604K/L604K mice died in utero. However, heterozygous animals were viable and displayed no overall increase in disease incidence, indicative of efficient compensation for the defective mutant polymerase. The life spans of wild-type and heterozygous Pold1 +/L604G mice did not differ, while that of Pold1 +/L604K mice was reduced by 18%. Cultured embryonic fibroblasts from the heterozygous strains exhibited comparable increases in both spontaneous mutation rate and chromosome aberrations. We observed no significant increase in cancer incidence; however, Pold1 +/L604K mice bearing histologically diagnosed tumors died at a younger median age than wild-type mice. Our results indicate that heterozygous mutation at L604 in the polymerase active site of DNA polymerase δ reduces life span, increases genomic instability, and accelerates tumorigenesis in an allele-specific manner, novel findings that have implications for human cancer.

Electron Microscopy and image analysis of nucleo-protein complexes

1994 ◽  
Vol 52 ◽  
pp. 88-89
Author(s):  
E. H. Egelman ◽  
X. Yu
Keyword(s):  
Electron Microscopy ◽  
Image Analysis ◽  
Normal Cell ◽  
Genetic Recombination ◽  
Protein Complexes ◽  
Chromosomal Rearrangements ◽  
Reca Protein ◽  
E Coli ◽  
Helical Polymer ◽  
Specific Protease

The RecA protein of E. coli has been shown to mediate genetic recombination, regulate its own synthesis, control the expression of other genes, act as a specific protease, form a helical polymer and have an ATPase activity, among other observed properties. The unusual filament formed by the RecA protein on DNA has not previously been shown to exist outside of bacteria. Within this filament, the 36 Å pitch of B-form DNA is extended to about 95 Å, the pitch of the RecA helix. We have now establishedthat similar nucleo-protein complexes are formed by bacteriophage and yeast proteins, and availableevidence suggests that this structure is universal across all of biology, including humans. Thus, understanding the function of the RecA protein will reveal basic mechanisms, in existence inall organisms, that are at the foundation of general genetic recombination and repair.Recombination at this moment is assuming an importance far greater than just pure biology. The association between chromosomal rearrangements and neoplasms has become stronger and stronger, and these rearrangements are most likely products of the recombinatory apparatus of the normal cell. Further, damage to DNA appears to be a major cause of cancer.

Meiotic chromosome behavior of Haworthia limifolia

2016 ◽  
Vol 5 (03) ◽  
pp. 4902
Author(s):  
Afrin Nazli ◽  
Kamini Kumar*
Keyword(s):  
Genetic Recombination ◽  
Meiotic Chromosome ◽  
Pollen Sterility ◽  
Meiotic Abnormalities ◽  
Chromosome Behavior ◽  
The Family ◽  
Medicinal Properties ◽  
Fruit Formation ◽  
Meiosis I ◽  
Chromosomal Behaviour

Haworthia limifolia is a xerophytic plant belonging to the family Liliaceae and is indigenous to Africa. It is use extensively for its medicinal properties like antibacterial, antifungal properties and used for the treatment of sores, superficial burns, as a blood purifier and to promote pregnancy in women and cattles. In present investigation chromosomal behaviour of H. limifolia in meiosis was studied. In diplotene stage chiasmata was observed showing the possibilities of genetic recombination. Chromosome clumps were observed in diakinesis indicating sticky nature of chromosomes. Meiotic abnormalities like stickiness, precocious movement, formation of bridges and laggards were also reported in both meiosis I and II. A fairly high percentage of pollen sterility that is 73.41% was recorded resulting in failure of fruit formation. This plant could be designated as facultative apomict (Swanson, 1957) as the only means of reproduction found was asexual or vegetative.

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