scholarly journals DNA mismatch detection using a pyrene–excimer-forming probe

2005 ◽  
pp. 2509 ◽  
Author(s):  
Kazushige Yamana ◽  
Yudai Fukunaga ◽  
Yusuke Ohtani ◽  
Sayaka Sato ◽  
Mitsunobu Nakamura ◽  
...  
Keyword(s):  
Dna Mismatch ◽  
Mismatch Detection

scholarly journals Evolutionary consequences of DNA mismatch inhibited repair opportunity.

Genetics ◽  
1992 ◽  
Vol 132 (2) ◽  
pp. 567-574
Author(s):  
W Stephan ◽  
C H Langley
Keyword(s):  
Molecular Evolution ◽  
Population Size ◽  
Rare Variants ◽  
Recombinational Repair ◽  
Strand Breaks ◽  
Dna Mismatch ◽  
Detection Systems ◽  
Slowing Down ◽  
Mismatch Detection ◽  
Evolutionary Consequences

Abstract Double strand breaks (DSBs) are often repaired via homologous recombination. Recombinational repair processes are expected to be influenced by nucleotide heterozygosity through mismatch detection systems. Unrepaired DSBs have severe biological consequences and are often lethal. We show that natural selection due to inhibition of recombinational repair associated with polymorphisms could influence their molecular evolution. The main conclusions from this analysis are that, for increasing population size, mismatch detection leads to a limit on average heterozygosity of otherwise selectively neutral polymorphism, an excess of rare variants, and a slowing down of the rate of neutral molecular evolution. The first two results suggest that mismatch detection may account for the surprisingly narrow range of observed average heterozygosities, given the great variation in population size between species.

scholarly journals Coupling Electrochemical Adsorption and Long‐range Electron Transfer: Label‐free DNA Mismatch Detection with Ultramicroelectrode (UME)

2019 ◽  
Vol 31 (11) ◽  
pp. 2232-2237
Author(s):  
Nivedita Basu ◽  
Thu Huong Ho ◽  
François‐Xavier Guillon ◽  
Yuanyuan Zhang ◽  
Pascal Bigey ◽  
...  
Keyword(s):  
Electron Transfer ◽  
Long Range ◽  
Label Free ◽  
Dna Mismatch ◽  
Mismatch Detection ◽  
Free Dna ◽  
Electrochemical Adsorption

scholarly journals MutL traps MutS at a DNA mismatch

2015 ◽  
Vol 112 (35) ◽  
pp. 10914-10919 ◽  
Author(s):  
Ruoyi Qiu ◽  
Miho Sakato ◽  
Elizabeth J. Sacho ◽  
Hunter Wilkins ◽  
Xingdong Zhang ◽  
...  
Keyword(s):  
Single Molecule ◽  
Conformational Changes ◽  
Thermus Aquaticus ◽  
Dna Mismatch ◽  
Sliding Clamp ◽  
Single Molecule Fret ◽  
Mismatch Detection ◽  
Current Thinking ◽  
Processivity Factor ◽  
Subsequent Activation

DNA mismatch repair (MMR) identifies and corrects errors made during replication. In all organisms except those expressing MutH, interactions between a DNA mismatch, MutS, MutL, and the replication processivity factor (β-clamp or PCNA) activate the latent MutL endonuclease to nick the error-containing daughter strand. This nick provides an entry point for downstream repair proteins. Despite the well-established significance of strand-specific nicking in MMR, the mechanism(s) by which MutS and MutL assemble on mismatch DNA to allow the subsequent activation of MutL’s endonuclease activity by β-clamp/PCNA remains elusive. In both prokaryotes and eukaryotes, MutS homologs undergo conformational changes to a mobile clamp state that can move away from the mismatch. However, the function of this MutS mobile clamp is unknown. Furthermore, whether the interaction with MutL leads to a mobile MutS–MutL complex or a mismatch-localized complex is hotly debated. We used single molecule FRET to determine that Thermus aquaticus MutL traps MutS at a DNA mismatch after recognition but before its conversion to a sliding clamp. Rather than a clamp, a conformationally dynamic protein assembly typically containing more MutL than MutS is formed at the mismatch. This complex provides a local marker where interaction with β-clamp/PCNA could distinguish parent/daughter strand identity. Our finding that MutL fundamentally changes MutS actions following mismatch detection reframes current thinking on MMR signaling processes critical for genomic stability.

DNA Mismatch Detection by Resonance Energy Transfer between Ruthenium(II) and Osmium(II) Tris(2,2‘-bipyridyl) Chromophores

2005 ◽  
Vol 44 (12) ◽  
pp. 4112-4114 ◽  
Author(s):  
Elena V. Bichenkova ◽  
Xuan Yu ◽  
Pranab Bhadra ◽  
Helena Heissigerova ◽  
Simon J. A. Pope ◽  
...  
Keyword(s):  
Energy Transfer ◽  
Resonance Energy Transfer ◽  
Resonance Energy ◽  
Dna Mismatch ◽  
Mismatch Detection

scholarly journals Electrocatalytic DNA mismatch detection

10.1038/80186 ◽  
2000 ◽  
Vol 18 (10) ◽  
pp. 1027-1027 ◽  
Author(s):  
Natalie DeWitt
Keyword(s):  
Dna Mismatch ◽  
Mismatch Detection

TUMOUR PATHOLOGY PREDICTS MICROSATELLITE INSTABILITY IN A POPULATION-BASED SERIES OF COLORECTAL CANCER CASES

2008 ◽  
Vol 31 (4) ◽  
pp. 12
Author(s):  
A J Hyde ◽  
D Fontaine ◽  
R C Green ◽  
M Simms ◽  
P S Parfrey ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lynch Syndrome ◽  
Microsatellite Instability ◽  
Population Based ◽  
Pathological Features ◽  
Predictive Tool ◽  
Entire Cohort ◽  
Dna Mismatch ◽  
Bethesda Guidelines ◽  
Revised Bethesda Guidelines

Background: Lynch Syndrome is an autosomal dominant trait that accounts forapproximately 3% of all cases of colorectal cancer (CRC). It is caused by mutations in DNA mismatch repair (MMR) genes, most commonly MLH1 or MSH2. These MMR defects cause high levels of microsatellite instability (MSI-H) in the tumours. MSI testing of all CRCs to identify potential Lynch Syndrome cases is not practical, so the Bethesda Guidelines, which use clinical and pathological features, were created to identify those tumours most likely to be MSI-H^1. In 2007 Jenkins et. al. created MsPath, a tool based on the pathological features described in the rarely used 3^rd Bethesda criterion, to improve prediction of MSI-H tumours among CRC cases diagnosed before age 60 years^2. Methods: We collected a population-based cohort of 716 CRC cases diagnosed before age 75 years in Newfoundland. For each of these cases we collected family history, performed MSI analysis, and scored a number of pathological features for the purpose of evaluating the accuracy of the Bethesda Criteria and MsPath at predicting MSI-H tumours. Results: Our work validates the MsPath tool in the Newfoundland population for the same age group used to create the tool. We found it identified MSI-H cases with a sensitivity of 95% and specificity of 35% in our population of CRCcases diagnosed before age 60 years (n=290). We also tested this tool on our older population of CRCcases, diagnosed at ages 60 to 74 years (n=426). We found it to be at least as predictive in this population,with a sensitivity of 95% and a specificity of 42%. We then used our entire cohort (N=716) to compare MsPath with the other Bethesda criteria.Bethesda criteria 1, 2, 4 and 5 together predicted MSI-H cases with a sensitivity of 67% and a specificity of 51%. MsPath was better at identifying these cases, with a sensitivity of 95% and a specificity of 39%. Conclusions: We conclude that MsPath can be extended to include patients diagnosed with CRC before age 75 years. As well, we have found that MsPath is a better predictive tool than the Revised Bethesda Guidelines for identifying MSI-H cases within a population-based setting of colorectal cancer. References: 1. Umar, A. et. al. J Natl Cancer Inst 2004;96:261-8 2.Jenkins, M.A. et. al. Gastroenterology 2007;133:48-56

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