Linked Life Data

21035467

Source:http://linkedlifedata.com/resource/pubmed/id/21035467

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1-2
pubmed:dateCreated
2010-12-27
pubmed:abstractText
DNA mismatch repair (MMR) maintains genomic integrity by correction of mispaired bases and insertion-deletion loops. The MMR pathway can also trigger a DNA damage response upon binding of MutS? to specific DNA lesions such as O(6)methylguanine (O(6)meG). Limited information is available regarding cellular regulation of these two different pathways. Within this report, we demonstrate that phosphorylated hMSH6 increases in concentration in the presence of a G:T mismatch, as compared to an O(6)meG:T lesion. TPA, a kinase activator, enhances the phosphorylation of hMSH6 and binding of hMutS? to a G:T mismatch, though not to O(6)meG:T. UCN-01, a kinase inhibitor, decreases both phosphorylation of hMSH6 and binding of hMutS? to G:T and O(6)meG:T. HeLa MR cells, pretreated with UCN-01 and exposed to MNNG, undergo activation of Cdk1 and mitosis despite phosphorylation of Chk1 and inactivating phosphorylation of Cdc25c. These results indicate that UCN-01 may inhibit an alternative cell cycle arrest pathway associated with the MMR pathway that does not involve Cdc25c. In addition, recombinant hMutS? containing hMSH6 mutated at an N-terminal cluster of four phosphoserines exhibits decreased phosphorylation and decreased binding of hMutS? to G:T and O(6)meG:T. Taken together, these results suggest a model in which the amount of phosphorylated hMSH6 bound to DNA is dependent on the presence of either a DNA mismatch or DNA alkylation damage. We hypothesize that both phosphorylation of hMSH6 and total concentration of bound hMutS? are involved in cellular signaling of either DNA mismatch repair or MMR-dependent damage recognition activities.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0027-5107
pubmed:author
pubmed:copyrightInfo
Copyright © 2010 Elsevier B.V. All rights reserved.
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
706
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
36-45
pubmed:dateRevised
2011-10-6
pubmed:meshHeading
pubmed-meshheading:21035467-Amino Acid Sequence, pubmed-meshheading:21035467-Animals, pubmed-meshheading:21035467-Base Pair Mismatch, pubmed-meshheading:21035467-Cell Line, pubmed-meshheading:21035467-Cell Line, Tumor, pubmed-meshheading:21035467-DNA, pubmed-meshheading:21035467-DNA Damage, pubmed-meshheading:21035467-DNA Mismatch Repair, pubmed-meshheading:21035467-DNA-Binding Proteins, pubmed-meshheading:21035467-Electrophoretic Mobility Shift Assay, pubmed-meshheading:21035467-HeLa Cells, pubmed-meshheading:21035467-Humans, pubmed-meshheading:21035467-Immunoblotting, pubmed-meshheading:21035467-Mice, pubmed-meshheading:21035467-Molecular Sequence Data, pubmed-meshheading:21035467-Mutation, pubmed-meshheading:21035467-NIH 3T3 Cells, pubmed-meshheading:21035467-Phosphorylation, pubmed-meshheading:21035467-Protein Binding, pubmed-meshheading:21035467-Protein Kinase Inhibitors, pubmed-meshheading:21035467-Serine, pubmed-meshheading:21035467-Signal Transduction, pubmed-meshheading:21035467-Spodoptera, pubmed-meshheading:21035467-Staurosporine
pubmed:year
2011
pubmed:articleTitle
Phosphorylated hMSH6: DNA mismatch versus DNA damage recognition.
pubmed:affiliation
Department of Biochemistry and Cancer Biology, University of Toledo College of Medicine, Toledo, OH 43614, USA. Saravanan_Kaliyaperumal@hms.harvard.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural