Ontology highlight
ABSTRACT:
PROVIDER: PRJEB36568 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR3867987_1.fastq.gz | Fastqsanger.gz | |||
| ERR3867987_2.fastq.gz | Fastqsanger.gz | |||
| ERR3867988_1.fastq.gz | Fastqsanger.gz | |||
| ERR3867988_2.fastq.gz | Fastqsanger.gz | |||
| ERR3867989_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 6 |
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Project description:An enduring issue in evolutionary and cancer biology is how replication infidelity influences genome composition and vice versa. Here we examine this issue by sequencing the genomes of diploid budding yeast strains that are either mismatch repair (MMR) proficient or deficient and encode wild type or mutator variants of the three major nuclear DNA replicases. Analysis of over 43,000 mutations that accumulated in the absence of selective pressure demonstrates that the nuclear DNA replication machinery generates less than one mismatch per genome and in combination with MMR, achieves a genome-wide per base error rate of 1.7 x 10-10. Absent both MMR and purifying selection, replication error patterns strongly depend on replication origin proximity, replication fork direction, and the local DNA sequence. Preferred sequences were observed for base substitutions and deletions. Error rates also vary with replication time, in linker versus nucleosome-bound DNA, in 5'- and 3'-untranslated regions, in coding regions and in intergenic DNA. This genome-wide view shows that replication fidelity is amazingly high but heterogeneous, in patterns that suggest the underlying mechanisms by which replication modulates genome stability and composition and vice versa. Six to ten isolates were sequenced for each combination of DNA polymerase (WT, pol1-L868M, pol2-M644G, pol3-L612M) and mismatch repair (proficient, deficient) genotypes. A single WT isolate was sequenced following micrococcal nuclease digestion.
2014-08-25 | E-GEOD-56939 | biostudies-arrayexpress
Project description:Inherited defects in the base-excision repair gene MBD4 predispose individuals to adenomatous polyposis and colorectal cancer, which is characterized by an accumulation of C>T transitions resulting from spontaneous deamination of 5’-methylcytosine. Despite its significance, this DNA repair pathway is still poorly understood. Here we show that the protein MBD4 is required for DNA methylation maintenance and G/T mismatch repair. Transcriptome and methylome analyses reveal a genome-wide hypomethylation of promoters, gene bodies and repetitive elements in the absence of MBD4 in vivo. Methylation mark loss is accompanied by a broad transcriptional derepression phenotype affecting promoters and retroelements with low methylated CpG density. MBD4 in vivo forms a complex with the mismatch repair proteins (MMR), which exhibits high bi-functional glycosylase/AP-lyase endonuclease specific activity towards methylated DNA substrates containing a G/T mismatch. Experiments using recombinant proteins reveal that the association of MBD4 with the MMR protein MLH1 is required for this activity. The described data identify MBD4 as an enzyme specifically designed to repair deaminated 5-methylcytosines and illustrates how MBD4 functions in normal and pathological conditions.
2022-01-10 | GSE84497 | GEO
Project description:Inherited defects in the base-excision repair gene MBD4 predispose individuals to adenomatous polyposis and colorectal cancer, which is characterized by an accumulation of C>T transitions resulting from spontaneous deamination of 5’-methylcytosine. Despite its significance, this DNA repair pathway is still poorly understood. Here we show that the protein MBD4 is required for DNA methylation maintenance and G/T mismatch repair. Transcriptome and methylome analyses reveal a genome-wide hypomethylation of promoters, gene bodies and repetitive elements in the absence of MBD4 in vivo. Methylation mark loss is accompanied by a broad transcriptional derepression phenotype affecting promoters and retroelements with low methylated CpG density. MBD4 in vivo forms a complex with the mismatch repair proteins (MMR), which exhibits high bi-functional glycosylase/AP-lyase endonuclease specific activity towards methylated DNA substrates containing a G/T mismatch. Experiments using recombinant proteins reveal that the association of MBD4 with the MMR protein MLH1 is required for this activity. The described data identify MBD4 as an enzyme specifically designed to repair deaminated 5-methylcytosines and illustrates how MBD4 functions in normal and pathological conditions.
2022-01-10 | GSE84319 | GEO
Project description:Inherited defects in the base-excision repair gene MBD4 predispose individuals to adenomatous polyposis and colorectal cancer, which is characterized by an accumulation of C>T transitions resulting from spontaneous deamination of 5’-methylcytosine. Despite its significance, this DNA repair pathway is still poorly understood. Here we show that the protein MBD4 is required for DNA methylation maintenance and G/T mismatch repair. Transcriptome and methylome analyses reveal a genome-wide hypomethylation of promoters, gene bodies and repetitive elements in the absence of MBD4 in vivo. Methylation mark loss is accompanied by a broad transcriptional derepression phenotype affecting promoters and retroelements with low methylated CpG density. MBD4 in vivo forms a complex with the mismatch repair proteins (MMR), which exhibits high bi-functional glycosylase/AP-lyase endonuclease specific activity towards methylated DNA substrates containing a G/T mismatch. Experiments using recombinant proteins reveal that the association of MBD4 with the MMR protein MLH1 is required for this activity. The described data identify MBD4 as an enzyme specifically designed to repair deaminated 5-methylcytosines and illustrates how MBD4 functions in normal and pathological conditions.
2022-01-10 | GSE84318 | GEO
Project description:In yeast, DNA breaks are usually repaired by homologous recombination (HR). An early step for HR pathways is formation of a heteroduplex, in which a single-strand from the broken DNA molecule pairs with a strand derived from an intact DNA molecule. If the two strands of DNA are not identical, there will be mismatches within the heteroduplex DNA (hetDNA). In wild-type strains, these mismatches are repaired by the mismatch repair (MMR) system, producing a gene conversion event. In strains lacking MMR, the mismatches persist. Most previous studies involving hetDNA formed during mitotic recombination were restricted to one locus. Below, we present a global mapping of hetDNA formed in the MMR-defective mlh1 strain. We find that many recombination events are associated with repair of double-stranded DNA gaps and/or involve Mlh1-independent mismatch repair. Many of our events are not explicable by the simplest form of the double-strand break repair model of recombination.
2017-06-27 | GSE100497 | 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: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
Project description:Objectives. Ovarian cancer (OC) is the eighth most common cancer and the eighth most common cause of cancer-related death in women. Identification of pathogenic variants in OC tissues is important to predict treatment response. This study aim to evaluate the mutational profile of a patient cohort, negative for BRCA1/2 germinal mutations and Mismatch Repair (MMR) defects, using next generation sequencing approach on DNA from formalin-fixed paraffin-embedded (FFPE) samples. We used a custom NGS panel, targeting 34 cancer related-genes, and analyzed NGS data to identify somatic and germline mutations in Italian patients affected by primary epithelia ovarian cancer.
2022-12-15 | E-MTAB-11133 | biostudies-arrayexpress
Project description:We performed proteogenomic analysis on a panel of 10 colorectal carcinoma cell lines with differences in DNA mismatch repair status (PMID:24247723).
2013-12-10 | MSV000078508 | MassIVE