scholarly journals Human mismatch repair system corrects errors produced during lagging strand replication more effectively

2016 ◽  
Author(s):  
Maria Andrianova ◽  
Georgii A Bazykin ◽  
Sergey Nikolaev ◽  
Vladimir Seplyarskiy
Keyword(s):  
Mismatch Repair ◽  
Mutation Rates ◽  
Repair System ◽  
Wild Type ◽  
Strand Asymmetry ◽  
Exonuclease Domain ◽  
Mismatch Repair System ◽  
Dna Strands ◽  
Leading Strand ◽  
Lagging Strand

Mismatch repair (MMR) is one of the main systems maintaining fidelity of replication. Different effectiveness in correction of errors produced during replication of the leading and the lagging DNA strands was reported in yeast, but this effect is poorly studied in humans. Here, we use MMR-deficient (MSI) and MMR-proficient (MSS) cancer samples to investigate properties of the human MMR. MSI, but not MSS, cancers demonstrate unequal mutation rates between the leading and the lagging strands. The direction of strand asymmetry in MSI cancers matches that observed in cancers with mutated exonuclease domain of polymerase δ, indicating that polymerase δ contributes more mutations than its leading-strand counterpart, polymerase ε. As polymerase δ primarily synthesizes DNA during the lagging strand replication, this implies that mutations produced in wild type cells during lagging strand replication are repaired by the MMR ~3 times more effectively, compared to those produced on the leading strand.

scholarly journals Human mismatch repair system balances mutation rates between strands by removing more mismatches from the lagging strand

2017 ◽  
Vol 27 (8) ◽  
pp. 1336-1343 ◽  
Author(s):  
Maria A. Andrianova ◽  
Georgii A. Bazykin ◽  
Sergey I. Nikolaev ◽  
Vladimir B. Seplyarskiy
Keyword(s):  
Mismatch Repair ◽  
Mutation Rates ◽  
Repair System ◽  
Mismatch Repair System ◽  
Lagging Strand

scholarly journals Saturation of DNA Mismatch Repair and Error Catastrophe by a Base Analogue in Escherichia coli

Genetics ◽  
2002 ◽  
Vol 161 (4) ◽  
pp. 1363-1371
Author(s):  
Kazuo Negishi ◽  
David Loakes ◽  
Roel M Schaaper
Keyword(s):  
Escherichia Coli ◽  
Mismatch Repair ◽  
Dna Mismatch Repair ◽  
Repair System ◽  
Mutagenic Action ◽  
Wild Type ◽  
Dna Mismatch ◽  
Cell Counts ◽  
Error Catastrophe ◽  
Mismatch Repair System

Abstract Deoxyribosyl-dihydropyrimido[4,5-c][1,2]oxazin-7-one (dP) is a potent mutagenic deoxycytidine-derived base analogue capable of pairing with both A and G, thereby causing G · C → A · T and A · T → G · C transition mutations. We have found that the Escherichia coli DNA mismatch-repair system can protect cells against this mutagenic action. At a low dose, dP is much more mutagenic in mismatch-repair-defective mutH, mutL, and mutS strains than in a wild-type strain. At higher doses, the difference between the wild-type and the mutator strains becomes small, indicative of saturation of mismatch repair. Introduction of a plasmid containing the E. coli mutL+ gene significantly reduces dP-induced mutagenesis. Together, the results indicate that the mismatch-repair system can remove dP-induced replication errors, but that its capacity to remove dP-containing mismatches can readily be saturated. When cells are cultured at high dP concentration, mutant frequencies reach exceptionally high levels and viable cell counts are reduced. The observations are consistent with a hypothesis in which dP-induced cell killing and growth impairment result from excess mutations (error catastrophe), as previously observed spontaneously in proofreading-deficient mutD (dnaQ) strains.

scholarly journals Frameshift intermediates in homopolymer runs are removed efficiently by yeast mismatch repair proteins.

1997 ◽  
Vol 17 (5) ◽  
pp. 2844-2850 ◽  
Author(s):  
C N Greene ◽  
S Jinks-Robertson
Keyword(s):  
Mismatch Repair ◽  
Wild Type Strain ◽  
Frameshift Mutation ◽  
Protein A ◽  
Repair System ◽  
Wild Type ◽  
Base Pairs ◽  
Replication Errors ◽  
Mismatch Repair System ◽  
Mismatch Repair Proteins

A change in the number of base pairs within a coding sequence can result in a frameshift mutation, which almost invariably eliminates the function of the encoded protein. A frameshift reversion assay with Saccharomyces cerevisiae that can be used to examine the types of insertions and deletions that are generated during DNA replication, as well as the editing functions that remove such replication errors, has been developed. Reversion spectra have been obtained in a wild-type strain and in strains defective for defined components of the postreplicative mismatch repair system (msh2, msh3, msh6, msh3 msh6, pms1, and mih1 mutants). Comparison of the spectra reveals that yeast mismatch repair proteins preferentially remove frameshift intermediates that arise in homopolymer tracts and indicates that some of the proteins have distinct substrate or context specificities.

scholarly journals Mismatch Repair in Escherichia coliCells Lacking Single-Strand Exonucleases ExoI, ExoVII, and RecJ

1998 ◽  
Vol 180 (4) ◽  
pp. 989-993 ◽  
Author(s):  
Reuben S. Harris ◽  
Kimberly J. Ross ◽  
Mary-Jane Lombardo ◽  
Susan M. Rosenberg
Keyword(s):  
Mismatch Repair ◽  
Single Strand ◽  
Mutation Rates ◽  
Repair System ◽  
Exonuclease Activity ◽  
Mismatch Repair System ◽  
Genes Encoding ◽  
Null Mutants

ABSTRACT In vitro, the methyl-directed mismatch repair system ofEscherichia coli requires the single-strand exonuclease activity of either ExoI, ExoVII, or RecJ and possibly a fourth, unknown single-strand exonuclease. We have created the first precise null mutations in genes encoding ExoI and ExoVII and find that cells lacking these nucleases and RecJ perform mismatch repair in vivo normally such that triple-null mutants display normal mutation rates. ExoI, ExoVII, and RecJ are either redundant with another function(s) or are unnecessary for mismatch repair in vivo.

LOCALIZED CONVERSION IN STREPTOCOCCUS PNEUMONIAE RECOMBINATION: HETERODUPLEX PREFERENCE

Genetics ◽  
1985 ◽  
Vol 110 (4) ◽  
pp. 557-568
Author(s):  
Michel Sicard ◽  
Jean-Claude Lefevre ◽  
Pezechpour Mostachfi ◽  
Anne-Marie Gasc ◽  
Claudine Sarda
Keyword(s):  
Recombination Frequency ◽  
Point Mutations ◽  
Repair System ◽  
Wild Type ◽  
Base Pairs ◽  
Present Evidence ◽  
Conversion System ◽  
Mismatch Repair System ◽  
Dna Strands

ABSTRACT In pneumococcal transformation the frequency of recombinants between point mutations is generally proportional to distance. We have recently described an aberrant marker in the amiA locus that appeared to enhance recombination frequency when crossed with any other allele of this gene. The hyperrecombination that we have observed in two-point crosses could be explained by two hypotheses: the aberrant marker induces frequent crossovers in its vicinity or the mutant is converted to wild type. In this report we present evidence showing that, in suitable three-point crosses, this hyperrecombination does not modify the recombination frequency between outside markers, suggesting that a conversion occurs at the site of this mutation. To estimate the length over which this event occurs, we isolated very closely linked markers and used them in two-point crosses. It appears that the conversion system removes only a few base pairs (from three to 27) around the aberrant marker. This conversion process is quite different from the mismatch-repair system controlled by hex genes in pneumococcus, which involves several thousand base pairs. Moreover, we have constructed artificial heteroduplexes using separated DNA strands. It appears that only one of the two heteroduplexes is specifically converted. The conversion system acts upon 5′..ATTAAT..3′/3′..TAAGTA..5′. A possible role of the palindrome resulting from the mutation is discussed.

Mismatch repair in recombination of bacteriophage T4

2012 ◽  
Vol 3 (6) ◽  
pp. 523-534
Author(s):  
Victor P. Shcherbakov
Keyword(s):  
Mismatch Repair ◽  
Bacteriophage T4 ◽  
Repair System ◽  
Recombination Mechanism ◽  
Replication Errors ◽  
Mismatch Repair System ◽  
Dna Strands ◽  
General Recombination ◽  
Recombination Pathway ◽  
Endonuclease Vii

AbstractThe review focuses on the mechanism of mismatch repair in bacteriophage T4. It was first observed in T4 as an extra recombination mechanism, which contributed to the general recombination only when particular rII mutations were used as genetic markers (high-recombination markers), whereas it was inactive toward other rII mutations (low-recombination markers). This marker-dependent recombination pathway was identified as a repair of mismatches in recombinational heteroduplexes. Comparison of the structure of markers enabled us to make several specific conclusions on the nature of the marker discrimination by the mismatch repair system operating during T4 crosses. First, heteroduplexes with one mismatched base pair (either of transition or of transversion type) as well as single-nucleotide mismatches of indel type are not efficiently repaired. Second, among the repairable mismatches, those with two or more contiguous mismatched nucleotides are the most effectively repaired, whereas insertion of one correct pair between two mismatched ones reduces the repairability. Third, heteroduplexes containing insertion mutations are repaired asymmetrically, the longer strand being preferentially removed. Fourth, the sequence environment is an important factor. Inspection of the sequences flanking mismatches shows that runs of A:T pairs directly neighboring the mismatches greatly promote repair. The mismatch is recognized by T4 endonuclease VII and nicked on the 3′ side. The nonpaired 3′ terminus is attacked by the proofreading 3′→5′ exonuclease of T4 DNA polymerase that removes the mismatched nucleotides along with several (~25) complementary nucleotides (the repair tract) and then switches to polymerization. The residual nick is ligated by DNA ligase (gp30). Most probably, the T4 system repairs replication and other mismatches as well; however, it might not discriminate old and new DNA strands and so does not seem to be aimed at repair of replication errors, in contrast to the most commonly studied examples of mismatch repair.

Conjugational Hyperrecombination Achieved by Derepressing the LexA Regulon, Altering the Properties of RecA Protein and Inactivating Mismatch Repair in Escherichia coli K-12

Genetics ◽  
2003 ◽  
Vol 163 (4) ◽  
pp. 1243-1254
Author(s):  
Vladislav A Lanzov ◽  
Irina V Bakhlanova ◽  
Alvin J Clark
Keyword(s):  
Escherichia Coli ◽  
Mismatch Repair ◽  
Reca Protein ◽  
Cumulative Effect ◽  
Fold Increase ◽  
Reca Gene ◽  
Repair System ◽  
Wild Type ◽  
Mismatch Repair System ◽  
K 12

Abstract The frequency of recombinational exchanges (FRE) that disrupt co-inheritance of transferred donor markers in Escherichia coli Hfr by F- crosses differs by up to a factor of two depending on physiological factors and culture conditions. Under standard conditions we found FRE to be 5.01 ± 0.43 exchanges per 100-min units of DNA length for wild-type strains of the AB1157 line. Using these conditions we showed a cumulative effect of various mutations on FRE. Constitutive SOS expression by lexA gene inactivation (lexA71::Tn5) and recA gene mutation (recA730) showed, respectively, ∼4- and 7-fold increases of FRE. The double lexA71 recA730 combination gave an ∼17-fold increase in FRE. Addition of mutS215::Tn10, inactivating the mismatch repair system, to the double lexA recA mutant increased FRE to ∼26-fold above wild-type FRE. Finally, we showed that another recA mutation produced as much SOS expression as recA730 but increased FRE only 3-fold. We conclude that three factors contribute to normally low FRE under standard conditions: repression of the LexA regulon, the properties of wild-type RecA protein, and a functioning MutSHL mismatch repair system. We discuss mechanisms by which the lexA, recA, and mutS mutations may elevate FRE cumulatively to obtain hyperrecombination.

scholarly journals The Escherichia coli Methyl-Directed Mismatch Repair System Repairs Base Pairs Containing Oxidative Lesions

2003 ◽  
Vol 185 (5) ◽  
pp. 1701-1704 ◽  
Author(s):  
Jennifer Wyrzykowski ◽  
Michael R. Volkert
Keyword(s):  
Escherichia Coli ◽  
Mismatch Repair ◽  
Spontaneous Mutation ◽  
Repair System ◽  
Dna Breaks ◽  
Base Pairs ◽  
Double Strand Dna Breaks ◽  
Hydrogen Peroxide Treatment ◽  
Mismatch Repair System ◽  
Dna Strands

ABSTRACT A major role of the methyl-directed mismatch repair (MMR) system of Escherichia coli is to repair postreplicative errors. In this report, we provide evidence that MMR also acts on oxidized DNA, preventing mutagenesis. When cells deficient in MMR are grown anaerobically, spontaneous mutation frequencies are reduced compared with those of the same cells grown aerobically. In addition, we show that a dam mutant has an increased sensitivity to hydrogen peroxide treatment that can be suppressed by mutations that inactivate MMR. In a dam mutant, MMR is not targeted to newly replicated DNA strands and therefore mismatches are converted to single- and double-strand DNA breaks. Thus, base pairs containing oxidized bases will be converted to strand breaks if they are repaired by MMR. This is demonstrated by the increased peroxide sensitivity of a dam mutant and the finding that the sensitivity can be suppressed by mutations inactivating MMR. We demonstrate further that this repair activity results from MMR recognition of base pairs containing 8-oxoguanine (8-oxoG) based on the finding that overexpression of the MutM oxidative repair protein, which repairs 8-oxoG, can suppress the mutH-dependent increase in transversion mutations. These findings demonstrate that MMR has the ability to prevent oxidative mutagenesis either by removing 8-oxoG directly or by removing adenine misincorporated opposite 8-oxoG or both.

scholarly journals Repair of single- and multiple-substitution mismatches during recombination in Streptococcus pneumoniae.

Genetics ◽  
1989 ◽  
Vol 121 (1) ◽  
pp. 29-36 ◽  
Author(s):  
A M Gasc ◽  
A M Sicard ◽  
J P Claverys
Keyword(s):  
Escherichia Coli ◽  
Streptococcus Pneumoniae ◽  
Mismatch Repair ◽  
Base Composition ◽  
Repair System ◽  
Wild Type ◽  
Simple Correlation ◽  
Repair Efficiency ◽  
Mismatch Repair System ◽  
Multiple Substitution

Abstract The use as genetic markers, during transformation of Streptococcus pneumoniae, of 19 sequences differing from wild type, located throughout the amiA locus, enabled us to examine the fate of 24 single- and 11 multiple-mismatches during recombination. Tentative mismatch ranking as a function of decreasing repair efficiency by the Hex mismatch repair system is G/T = A/C = G/G (maximum repair: 90-95%) greater than C/T (mostly 75 to 90% repair) greater than A/A (from 50 to 90% repair) greater than T/T (50-65% repair) greater than A/G (from 0 to 20% repair) greater than C/C. No indication of correction of the latter has been obtained. Over the limited number of samples examined, we observed no influence of the base composition of the surrounding sequence on correction efficiency for both transition mismatches and for G/G and C/C. Variations in the surrounding sequence affect repair of A/G and C/T, and, even more strongly, of A/A and T/T. No simple correlation to the G:C content of the surrounding sequence is apparent from our results, in contrast to the conclusion drawn for the Mut mismatch repair system of Escherichia coli. Examination of the fate of multiple mismatches suggests that C/C may sometimes impede recognition of otherwise corrected mismatches.

scholarly journals Competition between MutY and Mismatch Repair at A · C Mispairs In Vivo

2003 ◽  
Vol 185 (15) ◽  
pp. 4626-4629 ◽  
Author(s):  
Mandy Kim ◽  
Tiffany Huang ◽  
Jeffrey H. Miller
Keyword(s):  
Mismatch Repair ◽  
Hot Spot ◽  
Repair System ◽  
Wild Type ◽  
Mismatch Repair System ◽  
In The Wild

ABSTRACT We show that the MutY protein competes with the MutS-dependent mismatch repair system to process at least some A · C mispairs in vivo, converting them to G · C pairs. In the presence of an increased dCTP pool resulting from the loss of nucleotide diphosphate kinase, the frequency of A · T→G · C transitions at a hot spot in the rpoB gene is 30-fold lower in a MutY-deficient derivative than in the wild type.

Sign in / Sign up

Export Citation Format

Share Document