Evaluation of the MLH1 I219V alteration in DNA mismatch repair activity and ulcerative colitis

Inflammatory Bowel Diseases
Guido PlotzCarsten Schmidt

Abstract

Inflammatory bowel diseases (IBDs; ulcerative colitis, UC, and Crohn's disease, CD) show familial clustering suggestive of a genetic background. A linkage susceptibility region for these diseases (IBD9) lies on chromosome 3p and includes the DNA mismatch repair gene MLH1. Loss of MLH1 confers the characteristic microsatellite instability (MSI) phenotype which is also frequently found in the mucosa of IBD patients. A common germline alteration of MLH1 (655A>G) results in the amino acid exchange MLH1 I219V. Conflicting data exist on its effect on the function of the protein and it has recently been reported to cosegregate with refractory UC, suggesting that this alteration may impair mismatch repair activity and thereby contribute to certain forms of UC. We analyzed the MLH1 I219V alteration using in silico and biochemical analyses and assessed its appearance in 67 well-classified UC patients in comparison to 40 healthy individuals. The analyses showed that I219 is a conserved, buried hydrophobic residue, and that I219V is unlikely to abolish MLH1 function but may modulate it. Quantitative biochemical evaluation showed identical stability and activity of the protein. Furthermore, the alteration occurred equally frequently in anal...Continue Reading

References

Mar 1, 1990·Journal of Molecular Graphics·G Vriend
Sep 1, 1997·Nucleic Acids Research·S F AltschulD J Lipman
Mar 29, 2000·The Journal of Biological Chemistry·C Spampinato, P Modrich
Aug 19, 2000·Molecular Biotechnology·H Wang, J B Hays
Sep 21, 2001·American Journal of Human Genetics·J AltmüllerM Wjst
Mar 19, 2002·The Journal of Biological Chemistry·Guy TomerR Michael Liskay
Jun 11, 2002·American Journal of Physiology. Cell Physiology·Christina L ChangC Richard Boland
Jan 10, 2003·Nucleic Acids Research·John WestbrookHelen M Berman
Jun 12, 2003·Nucleic Acids Research·Guido PlotzStefan Zeuzem
Jun 26, 2003·Nucleic Acids Research·Ramu ChennaJulie D Thompson
Dec 19, 2003·Nucleic Acids Research·David L WheelerLukas Wagner
May 29, 2004·Gastroenterology·Tariq AhmadJean-Frédéric Colombel
Apr 25, 2006·Lancet·Daniel R GayaJack Satsangi
Jul 6, 2006·Journal of Molecular Histology·Guido PlotzJochen Raedle
Dec 1, 2006·Nucleic Acids Research·Guido PlotzJochen Raedle
Mar 22, 2007·Journal of the National Cancer Institute·Stavroula RaptisBharati Bapat
May 19, 2007·Cancer Research·Masanobu TakahashiChikashi Ishioka
Jun 8, 2007·Nature·UNKNOWN Wellcome Trust Case Control Consortium

❮ Previous
Next ❯

Citations

Apr 15, 2009·Biochemical and Biophysical Research Communications·Yuichiro TanakaKoichi Nakajima
Jun 28, 2012·Human Mutation·Ester BorràsGabriel Capellá
Sep 9, 2016·Frontiers in Oncology·Mev Dominguez-ValentinCarlos A Vaccaro
Apr 18, 2009·Genetic Testing and Molecular Biomarkers·Maria Teresa VietriMichele Cioffi
Jan 13, 2015·World Journal of Gastroenterology : WJG·Florian KuehnMichael Linnebacher

❮ Previous
Next ❯

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.

Related Papers

European Journal of Cancer : Official Journal for European Organization for Research and Treatment of Cancer (EORTC) [and] European Association for Cancer Research (EACR)
H FredrikssonJ Schleutker
© 2021 Meta ULC. All rights reserved