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The lysine‐specific methyltransferase KMT 2C/ MLL 3 regulates DNA repair components in cancer
Author(s) -
Rampias Theodoros,
Karagiannis Dimitris,
Avgeris Margaritis,
Polyzos Alexander,
Kokkalis Antonis,
Kanaki Zoi,
Kousidou Evgenia,
Tzetis Maria,
Kanavakis Emmanouil,
Stravodimos Konstantinos,
Manola Kalliopi N,
Pantelias Gabriel E,
Scorilas Andreas,
Klinakis Apostolos
Publication year - 2019
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201846821
Subject(s) - dna , methyltransferase , microbiology and biotechnology , lysine , biology , chemistry , genetics , methylation , amino acid
Genome‐wide studies in tumor cells have indicated that chromatin‐modifying proteins are commonly mutated in human cancers. The lysine‐specific methyltransferase 2C ( KMT 2C/ MLL 3) is a putative tumor suppressor in several epithelia and in myeloid cells. Here, we show that downregulation of KMT 2C 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 KMT 2C 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 PARP 1/2 for DNA repair, and treatment with the PARP 1/2 inhibitor olaparib leads to synthetic lethality, suggesting that cancer cells with low KMT 2C expression are attractive targets for therapies with PARP 1/2 inhibitors.