Related Experiment Video

Updated: Jan 30, 2026

Specificity Analysis of Protein Lysine Methyltransferases Using SPOT Peptide Arrays

Specificity Analysis of Protein Lysine Methyltransferases Using SPOT Peptide Arrays

Published on: November 29, 2014

The lysine-specific methyltransferase KMT2C/MLL3 regulates DNA repair components in cancer

Theodoros Rampias¹, Dimitris Karagiannis¹, Margaritis Avgeris²

¹Biomedical Research Foundation Academy of Athens, Athens, Greece.

|January 23, 2019

Abstract:

Genome-wide studies in tumor cells have indicated that chromatin-modifying proteins are commonly mutated in human cancers. The lysine-specific methyltransferase 2C (KMT2C/MLL3) is a putative tumor suppressor in several epithelia and in myeloid cells. Here, we show that downregulation of KMT2C in bladder cancer cells leads to extensive changes in the epigenetic status and the expression of DNA damage response and DNA repair genes. More specifically, cells with low KMT2C activity are deficient in homologous recombination-mediated double-strand break DNA repair. Consequently, these cells suffer from substantially higher endogenous DNA damage and genomic instability. Finally, these cells seem to rely heavily on PARP1/2 for DNA repair, and treatment with the PARP1/2 inhibitor olaparib leads to synthetic lethality, suggesting that cancer cells with low KMT2C expression are attractive targets for therapies with PARP1/2 inhibitors.

Insights

Low lysine-specific methyltransferase 2C (KMT2C) expression in bladder cancer impairs DNA repair, increasing genomic instability. This suggests KMT2C-deficient tumors are vulnerable to PARP1/2 inhibitors like olaparib.

Area of Science:

Oncology
Epigenetics
DNA Repair

Background:

Chromatin-modifying proteins are frequently mutated in human cancers.
Lysine-specific methyltransferase 2C (KMT2C/MLL3) is implicated as a tumor suppressor in various cell types.

Purpose of the Study:

To investigate the role of KMT2C in bladder cancer.
To determine the impact of KMT2C downregulation on DNA damage response and repair pathways.
To explore therapeutic vulnerabilities in KMT2C-deficient bladder cancer.

Main Methods:

Analysis of KMT2C expression and its effects on epigenetic status in bladder cancer cells.
Assessment of DNA damage response and repair gene expression.
Evaluation of homologous recombination deficiency and sensitivity to PARP1/2 inhibition.

Main Results:

Downregulation of KMT2C in bladder cancer cells alters epigenetic profiles and DNA repair gene expression.
Cells with low KMT2C activity exhibit homologous recombination deficiency and increased endogenous DNA damage.
Genomic instability is significantly higher in KMT2C-low bladder cancer cells.

Conclusions:

KMT2C deficiency compromises DNA repair, leading to genomic instability in bladder cancer.
Bladder cancer cells with low KMT2C expression are hypersensitive to PARP1/2 inhibitors.
Targeting KMT2C-deficient bladder cancers with PARP1/2 inhibitors like olaparib presents a promising therapeutic strategy.

Read full analysis

Keywords:

DNA repair KMT2C PARPi sensitivity epigenetic regulation

More Related Videos

Sequence-specific Labeling of Nucleic Acids and Proteins with Methyltransferases and Cofactor Analogues

Sequence-specific Labeling of Nucleic Acids and Proteins with Methyltransferases and Cofactor Analogues

Published on: November 22, 2014

Visualizing DNA Damage Repair Proteins in Patient-Derived Ovarian Cancer Organoids via Immunofluorescence Assays

Visualizing DNA Damage Repair Proteins in Patient-Derived Ovarian Cancer Organoids via Immunofluorescence Assays

Published on: February 24, 2023

Related Concept Videos

Overview of DNA Repair

Overview of DNA Repair

In order to be passed through generations, genomic DNA must be undamaged and error-free. However, every day, DNA in a cell undergoes several thousand to a million damaging events by natural causes and external factors. Ionizing radiation such as UV rays, free radicals produced during cellular respiration, and hydrolytic damage from metabolic reactions can alter the structure of DNA. Damages caused include single-base alteration, base dimerization, chain breaks, and cross-linkage.
Chemically...

Overview of DNA Repair

Overview of DNA Repair

Covalently Linked Protein Regulators

Covalently Linked Protein Regulators

Proteins can undergo many types of post-translational modifications, often in response to changes in their environment. These modifications play an important role in the function and stability of these proteins. Covalently linked molecules include functional groups, such as methyl, acetyl, and phosphate groups, and also small proteins, such as ubiquitin. There are around 200 different types of covalent regulators that have been identified.
These groups modify specific amino acids in a protein....

Mismatch Repair

Mismatch Repair

Base-pairing and DNA Repair

Base-pairing and DNA Repair

Nucleotide Excision Repair

Nucleotide Excision Repair

Articles linked to this work by shared authors, journal, and citation graph.

Targeting Collagens and LOX Through Plant-Derived MicroRNAs (XenomiRs).

Methods in molecular biology (Clifton, N.J.)·2026

Deciphering BAX and BCL2L12 circRNAs in Acute Myeloid Leukemia Through an Integrated Next-Generation and Nanopore Sequencing Approach.

Genes·2026

MicroRNAs in Breast Cancer: Biological Functions and Technologies for Experimental and Therapeutic Applications.

Cancers·2026

Liquid biopsy miRNA risk score in bladder cancer: Translational insights from patient-derived xenografts to prognostic stratification.

European journal of cancer (Oxford, England : 1990)·2026

Epigenetic silencing of miR-141 via core promoter methylation is associated with short-term bladder cancer progression.

The Journal of biological chemistry·2026

Wastewater genomic surveillance of SARS-CoV-2 by nanopore sequencing uncovers JN.1 prevalence and novel spike mutational hotspots in Athens during winter 2024-2025.

The Science of the total environment·2026

See all related articles