Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “frameshifting”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 973 records · Page 54Linked to original sources
PubMed2002

Comparative mutagenesis of the C8-guanine adducts of 1-nitropyrene and 1,6- and 1,8-dinitropyrene in a CpG repeat sequence. A slipped frameshift intermediate model for dinucleotide deletion.

In the Ames Salmonella typhimurium reversion assay 1,6- and 1,8-dinitropyrenes (1,6- and 1,8-DNPs) are much more potent mutagens than 1-nitropyrene (1-NP). Genetic experiments established that certain differences in the metabolism of the DNPs, which in turn result in increased DNA adduction, play a role. It remained unclear, however, if the DNP adducts, N-(guanin-8-yl)-1-amino-6 ()-nitropyrene (Gua-C8-1,6-ANP and Gua-C8-1,8-ANP), which contain a nitro group on the pyrene ring covalently linked to the guanine C8, are more mutagenic than the major 1-NP adduct, N-(guanin-8-yl)-1-aminopyrene (Gua-C8-AP). In order to address this, we have compared the mutation frequency of the three guanine C8 adducts, Gua-C8-AP, Gua-C8-1,6-ANP, and Gua-C8-1,8-ANP in a CGCG*CG sequence. Single-stranded M13mp7L2 vectors containing these adducts and a control were constructed and replicated in Escherichia coli. A remarkable difference in the induced CpG deletion frequency between these adducts was noted. In repair-competent cells the 1-NP adduct induced 1.7% CpG deletions without SOS, whereas the 1,6- and 1,8-DNP adducts induced 6.8 and 10.0% two-base deletions, respectively. With SOS, CpG deletions increased up to 1.9, 11.1, and 15.1% by 1-NP, 1,6-, and 1,8-DNP adducts, respectively. This result unequivocally established that DNP adducts are more mutagenic than the 1-NP adduct in the repetitive CpG sequence. In each case the mutation frequency was significantly increased in a mutS strain, which is impaired in methyl-directed mismatch repair, and a dnaQ strain, which carries a defect in proofreading activity of the DNA polymerase III. Modeling studies showed that the nitro group on the pyrene ring at the 8-position can provide additional stabilization to the two-nucleotide extrahelical loop in the promutagenic slipped frameshift intermediate through its added hydrogen-bonding capability. This could account for the increase in CpG deletions in the M13 vector with the nitro-containing adducts compared with the Gua-C8-AP adduct itself.

CpG Islands↗
PubMed1999

A Colombian family with X-linked juvenile retinoschisis with three affected females finding of a frameshift mutation.

X-linked retinoschisis (XLRS) is a vitreoretinal disease responsible for most cases of juvenile macular degeneration in males. Retinoschisis carrier females generally manifest no pathological symptoms. However, a large affected family from Colombia presented three affected females with typical RS phenotype similar to their 27 affected male relatives. Fundus examination as well as electroretinograms (ERG) indicate that the disease in these three affected females is as severe as in their affected male counterparts. DNA sequence analysis of the XLRS1 gene in the affected members of this family indicates a single base (G) deletion at the 639 base position (639delG). This deletion causes a frameshift during translation and results in a larger (235 amino acids) than normal peptide (224 amino acids) with grossly altered discoidin domain, which is considered critical for the cellular function of the protein. The co-segregation of this gene mutation with the RS phenotype and the RS carrier status as well as its complete absence in normal controls indicates that this genetic change is responsible for the RS pathology in this family. This (639delG) is a novel RS mutation and reported here for the first time. Furthermore, the analysis of the three affected females indicates that the RS pathology in affected females (a very rare occurrence) is due to XLRS1 mutations carried on both of their X chromosomes.

Adolescent↗
PubMed1985

Isolation of frameshift mutagens from smokers' urine: experiences with three concentration methods.

Frameshift mutagens were isolated and concentrated from cigarette smokers' urine by the use of three different extraction methods; XAD-2 resin chromatography, chloroform and blue cotton extraction systems. The extracts were tested for mutagenicity in the Salmonella/mammalian microsome test employing Salmonella typhimurium TA98. By the use of XAD-2 resin chromatography, no clear correlation was found between urine mutagenicity versus number of cigarettes smoked and no detectable mutagenic activity was observed when fewer than four cigarettes a day were consumed. A clear correlation was found between urine mutagenicity versus number of cigarettes smoked when urine samples were extracted by the use of chloroform or blue cotton. Interference of free histidine in mutagenicity assays could be excluded.

Adult↗
PubMed1983

New suppressors of frameshift mutations in Salmonella typhimurium.

Several new types of suppressor mutants have been isolated. These were identified among revertants of mutants originally generated by mutagens other than the acridine-derived ICR191. The new suppressors correct mutations other than those with runs of C or G which are recognized by the previously described suppressors. Several frameshift mutations are corrected by more than one suppressor type. Apparently, the DNA base sequence near these mutant sites includes sites of action for several distinct suppressor types.

Base Sequence↗
PubMed1988

Evidence for frameshift mutations in the hisH gene of Escherichia coli causing synthesis of a partially active glutamine amidotransferase.

Among eight strains carrying acridine-induced mutations in hisH, five which mapped at four different sites in the promoter-distal region of the gene showed His+ phenotypes on media containing a purine. By complementation analysis, hisH enzyme was shown to be required for growth on purines. Purine-sensitive His+ revertants of strains able to grow on purines carried second-site mutations which in one case could be shown to map in hisG. Strains able to grow on purines were able to grow on 2-thiazolyl-DL-alanine, too. We conclude that frameshift mutations in the promoter-distal part of the hisH gene of E. coli do not completely abolish the activity of the gene product.

Anthranilate Synthase↗
PubMed1997

A translation frameshift mutation induced by a cytosine insertion in the polycystic kidney disease 2 gene (PDK2).

Mutations in the PKD2 gene on the long arm of chromosome 4 are responsible for approximately 15% of cases of polycystic kidney disease. Perhaps the only difference from the more common ADPKD1 cases is the rate of progression of cystic changes, and the age of onset, which is 10-15 years later for the ADPKD2 form. In Cyprus there are at least three large families, documented by molecular linkage analysis, that map to the PKD2 locus. For two of them the defects were recently shown to be nonsense mutations at positions arginine 742 and glutamine 405. In this report, we describe the mutation in the third family, CY1602. For this, the entire coding sequence was systematically screened by single strand conformation analysis and heteroduplex formation. A novel mutation was identified in exon 2 where a new cytosine residue was inserted immediately after codon 231 (231insC). It causes a translation frameshift and is expected to lead to the introduction of 37 novel amino acids before the translation reaches a new STOP codon. It is the most amino terminal mutation reported to date, and based on the protein's modeled structure, is predicted to be within the first transmembrane domain. It is the fourth PKD2 mutation reported thus far, and the first which is not a nonsense mutation.

Cytosine↗
PubMed1986

Enhancement of frameshift mutagenesis in Salmonella typhimurium derivatives of hisC3076 by 5-azacytidine and other agents.

The yield of frameshift revertants of Salmonella typhimurium strain hisC3076 on plates containing the mutagen 9-aminoacridine (9AA) is enhanced by the addition to the selection medium of a number of chemical agents. These include 5-azacytidine (5-azaC), naladixic acid, ethyl methanesulphonate; pre-treatment of cells with u.v. light or gamma-radiation is also effective. With the exception of u.v. which is detected as a poor mutagen in strain hisC3076, all other enhancing agents are not usually detected as mutagens in this strain. The observed synergism between 9AA and 5-azaC in recA and uvrB derivatives of hisC3076 eliminates the possibility that recA-dependent repair or excision repair is necessary. However a lack of synergism in a uvrD derivative suggests that helicase II is involved. It is suggested that the presence of 9AA in the plating medium enables the synergistic agents to be detected as mutagens.

Aminacrine↗
PubMed1983

A frameshift addition causes silencing of the delta-globin gene in an old world monkey, an anubis (Papio doguera).

A delta-globin gene of an anubis, Papio doguera, was cloned, and the nucleotide sequence of a region of about 2,000 bp including the gene was determined. In comparison with that of pSP3, a delta-globin clone from the gene library of a normal Japanese, the anubis delta-globin gene showed one base addition in the second exon at the codon for amino acid 55, generating a termination codon at the new 59th codon. The other differences found in the region analyzed were not considered to affect expression of the delta-globin gene. Therefore, it was concluded that this frameshift addition was at least one of the causes of silencing of the delta-globin gene in the anubis. In addition, from the sequence divergence in the delta-globin gene, the period of this silencing was estimated to be at most 4 million years, and the divergence of anubis occurred at most 30 million years ago.

Animals↗
PubMed1987

The nucleotide sequence of a 3.2 kb segment of mitochondrial maxicircle DNA from Crithidia fasciculata containing the gene for cytochrome oxidase subunit III, the N-terminal part of the apocytochrome b gene and a possible frameshift gene; further evidence for the use of unusual initiator triplets in trypanosome mitochondria.

A 3.2 kb segment of the maxicircle of Crithidia fasciculata mitochondrial (mt) DNA contains the gene for cytochrome oxidase subunit III (coxIII), the N-terminal portion of the gene for apocytochrome b (cytb) and two partially overlapping Unassigned Reading Frames (C.URF2/1). Transcript analysis of the segment reveals that both the coxIII gene and the C.URF2/1 area are transcribed into a pair of RNA products. With the C. fasciculata gene version as a probe, a coxIII gene could not be detected in nuclear and mtDNA of Trypanosoma brucei, indicating that the cytochrome oxidases of these two closely related trypanosome species may differ. The nucleotide homology in the N-terminal region of the coxIII and cytb genes in T. brucei, Leishmania tarentolae and C. fasciculata starts at a UUA leucine codon, which adds further support to the hypothesis that apart from AUG, other initiator triplets are used in trypanosomal mitochondria: UUG, CUG and UUA, all triplets coding for leucine in the universal code. Finally, the possibility is discussed that the two overlapping URFs (C.URF2/1) in fact represent a single, frameshift containing, gene.

Amino Acid Sequence↗
PubMed1990

Frameshift suppression at tandem AGA and AGG codons by cloned tRNA genes: assigning a codon to argU tRNA and T4 tRNA(Arg).

Arginine is coded for by CGN (N = G, A, U, C), AGA and AGG. In Escherichia coli there is little tRNA for AGA and AGG and the use of these codons is strongly avoided in virtually all genes. Recently, we demonstrated that the presence of tandem AGA or AGG codons in mRNA causes frameshifts with high frequency. Here, we show that phaseshifts can be suppressed when cells are transformed with the gene for tRNA(T4Arg) or E. coli tRNA(argU,Arg) demonstrating that such errors are the result of tRNA depletion. Bacteriophage T4 encoded tRNA(Arg) (anticodon UCU) corrects shifts at AGA-AGA but not at AGG-AGG, suggesting that this tRNA can only read AGA. Similarly, comparison of the translational efficiencies in an argU (Ts) mutant and in its isogenic wild type parent indicates that argU tRNA (anticodon UCU) reads AGA but not AGG. An argU (Ts) mutant barely reads through AGA-AGA at 42 degrees C but translation of AGG-AGG is hardly, if at all, affected. Overexpression of argU+ relaxes the codon specificity. The thermosensitive mutant in argU, previously called dnaY because it is defective in DNA replication, can be complemented for growth by the gene for tRNA(T4Arg). This implies that the sole function of the argU gene product is to sustain protein synthesis and that its role in replication is probably indirect.

Base Sequence↗
PubMed2003

Structural study of DNA duplex containing an N-(2-deoxy-beta-D-erythro-pentofuranosyl) formamide frameshift by NMR and restrained molecular dynamics.

The presence of an N-(2-deoxy-beta-D-erythro-pentofuranosyl) formamide (F) residue, a ring fragmentation product of thymine, in a frameshift context in the sequence 5'-d-(AGGACCACG)*d(CGTGGFTCCT) has been studied by 1H and 31P nuclear magnetic resonance (NMR) and molecular dynamics. Two-dimensional NMR studies show that the formamide residue, whether the cis or trans isomer, is rotated out of the helix and that the bases on either side of the formamide residue in the sequence, G14 and T16, are stacked over each other in a way similar to normal B-DNA. The cis and trans isomers were observed in the ratio 3:2 in solution. Information extracted from 31P NMR data reveal a modification of the phosphodiester backbone conformation at the extrahelical site, which is also observed during the molecular dynamics simulations.

Base Sequence↗
PubMed2025

Translational reading frame determines the pathogenicity of C-terminal frameshift deletions in MeCP2: an alternative therapeutic approach.

Mutations in the MECP2 gene cause the severe neurological disorder Rett syndrome. A cluster of frameshift-causing C-terminal deletions (CTDs) lead to loss of ~100 amino acids at the C-terminus of the MeCP2 protein, and account for approximately 10% of RTT-causing mutations. The pathogenicity of C-terminal deletions (CTDs) is unexpected, as this C-terminal domain is non-essential in mice. Utilising databases of pathogenic and benign human MECP2 mutations, we find that some individuals with apparently typical CTDs do not exhibit Rett syndrome, confirming that C-terminal truncations are not intrinsically pathogenic. Using human DNA sequence data and mouse models, we demonstrate that pathogenicity results from a drastic reduction in MeCP2 levels and is determined by the presence of the short amino acid motif proline-proline-stop (-PPX) at the C-terminus, which results from a shift to the +2 reading frame. Individuals with CTDs that shift to the +1 frame avoid this motif and do not develop Rett syndrome. Mutating the stop codon of the PPX motif to tryptophan rescues MeCP2 expression and RTT-like phenotypes in a CTD mouse model. Finally, we demonstrate that an adenine base editor can efficiently introduce this tryptophan substitution in cultured cells. Overall, our findings uncover a simple and reliable prognostic distinction between benign and pathogenic CTDs and provide proof-of-concept for an editing strategy that potentially corrects all disease-causing CTD mutations.

Journal Article↗
PubMed1992

Frameshifting in the expression of the Escherichia coli trpR gene.

The trpR gene of Escherichia coli carries an open reading frame that encodes the trp repressor, 108 amino acids long. Here we show that translation of an additional (+1) reading frame of trpR occurs both in vivo and in vitro. This results in the synthesis of a stable +1 frame polypeptide. Using site-specific mutagenesis, immunological techniques and amino acid sequencing we have found that the N-terminus of the +1 frame product and that of the known 0 frame product are identical but that their C-termini differ. Our results are discussed in relation to the role of natural frameshifting as a regulatory mechanism of gene expression in general, and with respect to tryptophan biosynthesis in particular.

Amino Acid Sequence↗
PubMed1989

Prevention of translational frameshifting by the modified nucleoside 1-methylguanosine.

The methylated nucleoside 1-methylguanosine (m1G) is present next to the 3' end of the anticodon (position 37) in all transfer RNAs (tRNAs) that read codons starting with C except in those tRNAs that read CAN codons. All of the three proline tRNA species, which read CCN codons in Salmonella typhimurium, have been sequenced and shown to contain m1G in position 37. A mutant of S. typhimurium that lacks m1G in its tRNA when grown at temperatures above 37 degrees C, has now been isolated. The mutation (trmD3) responsible for this methylation deficiency is in the structural gene (trmD) for the tRNA(m1G37)methyltransferase. Therefore, the three proline tRNAs in the trmD3 mutant have an unmodified guanosine at position 37. Furthermore, the trmD3 mutation also causes at least one of the tRNAPro species to frequently shift frame when C's are present successively in the message. Thus, m1G appears to prevent frameshifting. The data from eubacteria apply to both eukaryotes and archaebacteria.

Anticodon↗
PubMed1969

Externally suppressible frameshift mutant of Salmonella typhimurium.

Prototrophic revertants of ICR-191A-induced frameshift mutant hisD3018 have been induced spontaneously by ICR-191A and N-methyl-N'-nitro-N-nitrosoguanidine (NG) treatment. In each case two genetically distinct prototroph classes were differentiated by transducibility into his deletion recipients: (i) transducible, generally fast-growing revertants within the hisD gene producing from 10 to 100% of normal amounts of histidinol dehydrogenase and (ii) nontransducible slow-growing prototrophs with very low levels of enzyme activity of which at least some arose by external suppression. These nontransducible revertants, whether arising spontaneously or in the presence of ICR-191A or NG, contain histidinol dehydrogenase which is electrophoretically similar to the wild-type enzyme.

Acridines↗
PubMed1989

Genetic characterization of frameshift suppressors with new decoding properties.

Suppressor mutants that cause ribosomes to shift reading frame at specific and new sequences are described. Suppressors for trpE91, the only known suppressible -1 frameshift mutant, have been isolated in Escherichia coli and in Salmonella typhimurium. E. coli hopR acts on trpE91 within the 9-base-pair sequence GGA GUG UGA, is dominant, and is located at min 52 on the chromosome. Its Salmonella homolog maps at an equivalent position and arises as a rarer class in that organism as compared with E. coli. The Salmonella suppressor, hopE, believed to be in a duplicate copy of the same gene, maps at min 17. The +1 suppressor, sufT, acts at the nonmonotonous sequence CCGU, is dominant, and maps at min 59 on the Salmonella chromosome.

Base Sequence↗
PubMed1991

Ribosome hopping and translational frameshifting are inadequate alternatives to translational attenuation in cat-86 regulation.

The induction of cat-86 by chloramphenicol has been proposed to follow the translational attenuation model. In the absence of inducer, the cat-86 gene is transcribed but remains phenotypically unexpressed because the transcripts sequester the ribosome binding site for the cat coding sequence in a stable stem-loop structure, preventing translation initiation. The translational attenuation model proposes that the natural inducer, chloramphenicol, stalls a ribosome in the leader region of cat transcripts, which causes localized melting of the downstream stem-loop structure, allowing initiation of translation of the cat-86 coding sequence. Although it is established that ribosome stalling in the cat-86 leader can induce translation of the coding sequence, several subsequent steps predicted by the model remain to be experimentally confirmed. As a consequence, the present evidence for cat-86 regulation can also be explained by two other potential control devices, ribosome hopping and translational frameshifting. Here we describe experiments designed to determine whether the alternatives to translational attenuation regulate cat-86. The results obtained are inconsistent with both competing models and are consistent with predictions made by the translational attenuation model.

Bacillus subtilis↗
PubMed1995

Properties of peptide chain release factor 2 from Streptomyces coelicolor A3(2): conserved primary structure but no frameshift regulation.

A gene was cloned from Streptomyces coelicolor A3(2). It encodes a protein of 368 amino acid residues with a high degree of similarity to prokaryotic release factor 2. However, it has neither an internal stop codon nor the Shine-Dalgarno-like sequence immediately upstream of the assumed frameshift position. The gene is expressed and functional in Escherichia coli as peptide chain release factor 2. The transcription start site is at or adjacent to the translational start site. The size of the mRNA detected by hybridization suggests that the gene (prfB) is monocistronic in S. coelicolor A3(2). However, about 80 bp upstream of the gene there is an operon which is composed of two genes encoding eukaryotic-type serine/threonine kinases.

Amino Acid Sequence↗