The lysine-specific methyltransferase KMT2C/MLL3 regulates DNA repair components in cancer. Academic Article uri icon

Overview

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.

publication date

  • January 21, 2019

Research

keywords

  • DNA Repair
  • DNA-Binding Proteins
  • Neoplasms

Identity

PubMed Central ID

  • PMC6399616

Scopus Document Identifier

  • 85060335352

Digital Object Identifier (DOI)

  • 10.15252/embr.201846821

PubMed ID

  • 30665945

Additional Document Info

volume

  • 20

issue

  • 3