The molecular mechanism of DNA damage recognition by MutS homologs and its consequences for cell death response.

Nucleic Acids Research
Freddie R SalsburyKarin D Scarpinato

Abstract

We determined the molecular mechanism of cell death response by MutS homologs in distinction to the repair event. Key protein-DNA contacts differ in the interaction of MutS homologs with cisplatinated versus mismatched DNA. Mutational analyses of protein-DNA contacts, which were predicted by molecular dynamics (MD) simulations, were performed. Mutations in suggested interaction sites can affect repair and cell death response independently, and to different extents. A glutamate residue is identified as the key contact with cisplatin-DNA. Mutation of the residue increases cisplatin resistance due to increased non-specific DNA binding. In contrast, the conserved phenylalanine that is instrumental and indispensable for mismatch recognition during repair is not required for cisplatin cytotoxicity. These differences in protein-DNA interactions are translated into localized conformational changes that affect nucleotide requirements and inter-subunit interactions. Specifically, the ability for ATP binding/hydrolysis has little consequence for the MMR-dependent damage response. As a consequence, intersubunit contacts are altered that most likely affect the interaction with downstream proteins. We here describe the interaction of MutS ho...Continue Reading

References

Aug 25, 1987·Nucleic Acids Research·W N HunterO Kennard
Feb 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·J V SkellyS Neidle
Feb 1, 1996·Journal of Molecular Graphics·W HumphreyK Schulten
Jul 17, 2001·The Journal of Biological Chemistry·L J BlackwellP Modrich
Jul 27, 2001·Nucleic Acids Research·N K Banavali, A D MacKerell
Oct 17, 2001·The Journal of Biological Chemistry·M J SchofieldP Hsieh
Oct 20, 2001·The Journal of Biological Chemistry·K DrotschmannT A Kunkel
Jul 13, 2002·Expert Review of Anticancer Therapy·J A Irving, A G Hall
Dec 31, 2002·Proceedings of the National Academy of Sciences of the United States of America·Niu HuangAlexander D MacKerell
Jan 2, 2003·DNA Repair·Karin DrotschmannThomas A Kunkel
Jan 30, 2003·The EMBO Journal·Meindert H LamersTitia K Sixma
Feb 26, 2003·Proceedings of the National Academy of Sciences of the United States of America·Hideki ShimodairaJean Y J Wang
Mar 8, 2003·The Journal of Biological Chemistry·Keith P Bjornson, Paul Modrich
Nov 25, 2003·Proceedings of the National Academy of Sciences of the United States of America·Hong WangDorothy A Erie
Jan 28, 2004·Cancer Research·Diana P LinWinfried Edelmann
Apr 24, 2004·The Journal of Biological Chemistry·Diana MartikPaul Modrich
Jul 21, 2004·Journal of Computational Chemistry·Alexander D Mackerell
Sep 18, 2004·Cancer Research·Ekaterina BassettMarila Cordeiro-Stone
Jun 11, 2005·Nucleic Acids Research·Jill E ClodfelterKarin Drotschmann
Oct 11, 2005·DNA Repair·John B HaysHuixian Wang
Feb 24, 2006·Environmental and Molecular Mutagenesis·Huxian WangJohn B Hays

❮ Previous
Next ❯

Citations

Feb 26, 2010·Biochemistry·Lauryn E SassDorothy A Erie
Oct 16, 2008·The Journal of Biological Chemistry·Ingrid TessmerDorothy A Erie
Mar 17, 2009·The Journal of Biological Chemistry·Ryan P ToppingKarin Drotschmann Scarpinato
Jan 3, 2012·Journal of Biomolecular Structure & Dynamics·Lacramioara Negureanu, Freddie R Salsbury
Jun 21, 2012·Journal of Biomolecular Structure & Dynamics·Lacramioara Negureanu, Freddie R Salsbury
Jul 30, 2010·Mutation Research·Yaroslava Y Polosina, Claire G Cupples
Oct 12, 2010·Journal of Nucleic Acids·Aksana VasilyevaKarin D Scarpinato
Oct 24, 2006·Cancer Treatment Reviews·Anna Maria ValentiniMaria L Caruso
Dec 3, 2009·BioEssays : News and Reviews in Molecular, Cellular and Developmental Biology·Yaroslava Y Polosina, Claire G Cupples
Dec 19, 2012·Structure·Bjørn DalhusMagnar Bjørås
Oct 4, 2011·Biophysical Journal·Susan N PieniazekD L Beveridge
Nov 10, 2011·Biophysical Journal·Sean M Law, Michael Feig
Jun 17, 2016·Journal of the American Chemical Society·Cheng TanShoji Takada
Oct 22, 2016·PLoS Computational Biology·Beibei WangMichael Feig
Dec 25, 2007·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Joanna WillDirk Wolters
May 21, 2008·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Maria Castellano-CastilloViktor Brabec
Aug 18, 2017·Journal of Biomolecular Structure & Dynamics·Ryan C GodwinFreddie R Salsbury
Mar 1, 2017·Frontiers of Physics·Ryan L MelvinFreddie R Salsbury
Nov 16, 2019·Advanced Theory and Simulations·Christopher MaffeoAleksei Aksimentiev
May 26, 2017·Cellular Oncology (Dordrecht)·Christiane RudolphAnne Jørgensen
Aug 12, 2017·Protein Science : a Publication of the Protein Society·Ryan L MelvinFreddie R Salsbury
Mar 18, 2008·Journal of the American Chemical Society·Danielle A PfaffTammy J Dwyer
Nov 2, 2016·Journal of Chemical Theory and Computation·Ryan L MelvinFreddie R Salsbury

❮ Previous
Next ❯

Methods Mentioned

BETA
X-ray

Software Mentioned

visual molecular dynamics ( VMD )
NAMD
VMD
CHARMM

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.