Transcriptomic evaluation of mismatch repair defects
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ABSTRACT:
PROVIDER: PRJNA489879 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:Using numerous isogenic models of mismatch repair defects we sought to understand how these defects influence global transcription
2018-09-08 | GSE119667 | GEO
Project description:Biases of DNA repair can shape the nucleotide landscape of genomes at evolutionary timescales. However, such biases have not yet been measured in chromatin for lack of technologies. Here we develop a genome-wide assay whereby the same DNA lesion is repaired in different chromatin contexts. We insert thousands of barcoded transposons carrying a reporter of DNA mismatch repair in the genome of mouse embryonic stem cells. Upon inducing a double-strand break between tandem repeats, a mismatch is generated when the single strand annealing repair pathway is used. Surprisingly, the mismatch repair machinery favors the same strand 60-80% of the time. The location of the lesion in the genome and the type of mismatch have little influence on the repair bias in this context.
2020-05-14 | GSE141211 | GEO
Project description:The mismatch repair (MMR) family is a highly conserved group of proteins that function in correcting base-base and insertion-deletion mismatches generated during DNA replication. To systematically investigate the mismatch repair pathway, we conducted a proteomic analysis and identified MMR-associated protein complexes using a tandem-affinity purification coupled with mass spectrometry (TAP-MS) method. In total, we identified 262 high-confidence candidate interaction proteins (HCIPs).
2016-02-08 | PXD003014 | Pride
Project description:Mismatch repair gene sequencing of sebaceous neoplasia
| PRJEB79223 | ENA
Project description:DNA mismatch repair (MMR) is an evolutionarily conserved process that corrects innate DNA polymerase infidelities during replication to maintain genomic integrity. Defects in a subset of MMR genes are associated with hereditary non-polyposis colon cancer and some other sporadic cancers, highlighting the crucial role for MMR in genome maintenance. In E. coli a helicase implicated in the MMR process is well characterized, and named UvrD, whereas in mammals it has not been identified yet, even though the eukaryotic DNA mismatch pathway is analogous to the bacterial one and uses a similar repair mechanism and key components. Here we identify MCM9 as a helicase playing a vital role in MMR in mammals. MCM9 is the last discovered member of the MCM2-9 family, and has been implicated in replication and homologous recombination processes. By an affinity-purification proteomic approach, we found that MCM9 interacts with the MMR initiation complex. Immortalized cells from MCM9 knockout mice showed clear length alterations in their microsatellites, and a dramatic MMR deficiency compared to wild-type cells. We also found that a helicase-dead form of MCM9 is totally unable to restore the MMR deficiency phenotype. Furthermore, using an siRNA approach in human cells, we demonstrated that MCM9 is regulated by MSH2, a protein responsible for mismatch recognition. Our results clearly reveal that MCM9 functions as a helicase for DNA mismatch repair in mammals, and thus is essential for the maintenance of genome stability. Proteomics analysis: FLAG-HA-tagged human MCM9 plus associated proteins were isolated by tandem affinity purification from nuclear extracts of stably-expressing HeLa S3 cells, then analysed by SDS-PAGE and silver staining. Gel lanes were cut into slices, which were processed and analysed separately. Proteins in each gel slice were digested with trypsin, extracted and analysed by LC-MS/MS on a Thermo Scientific LTQ Velos mass spectrometer, generating a series of MS RAW files. Bioinformatics: Peptide and protein identification from MS data was performed using the Sequest program, with a human IPI sequence database (v.3.60). Trypsin was defined as the protease used, a peptide mass tolerance of 2.5 was specified, and all peptide matches have a Sequest Xcorr score ≥0.5.
2015-08-19 | PXD000212 | Pride
Project description:The mismatch repair (MMR) family is a highly conserved group of proteins that function in correcting base-base and insertion-deletion mismatches generated during DNA replication. To systematically investigate the mismatch repair pathway, we conducted a proteomic analysis and identified MMR-associated protein complexes using a tandem-affinity purification coupled with mass spectrometry (TAP-MS) method. In total, we identified 262 high-confidence candidate interaction proteins (HCIPs).
2016-03-13 | MSV000079578 | MassIVE
Project description:Using in vitro directed evolution, we show that mismatch repair-deficient Pseudomonas aeruginosa can engage novel resistance mechanisms to ceftazidime-avibactam.
2021-08-30 | GSE180086 | GEO
Project description:Mouse models of mismatch repair deficiency
| PRJEB56609 | ENA
Project description:We used Affymetrix microarrays to determine the cisplatin-induced gene expression changes in E. coli deficient in dam and mismatch repair (dam, dam mutS, and mutS mutant strains). E. coli deficient in dam are hypersensitive to cisplatin. However introducing an additional mutation in mismatch repair (i.e., a mutation in mutS or mutL) abrogates this sensitivity and essentially restores wildtype levels of resistance. Keywords: Drug-induced expression
2005-07-27 | GSE2999 | GEO
Project description:This clinical trial evaluates the effect of tislelizumab in treating patients with mismatch repair deficient endometrial cancer that has come back (recurrent). Deoxyribonucleic acid (DNA) mismatch repair (MMR) is a system for recognizing and repairing DNA errors and damage. Mismatch repair deficient tumors (dMMR) may have difficulty repairing DNA mutations during replication that may affect tumor’s response to therapy. Immunotherapy with monoclonal antibodies, such as tislelizumab, may help the body’s immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving tislelizumab may help treat patients with mismatch repair deficient endometrial cancer.
| 2379033 | ecrin-mdr-crc