JAK2 regulates mismatch repair protein-mediated epigenetic alterations in response to oxidative damage.

ABSTRACT: At sites of chronic inflammation epithelial cells undergo aberrant DNA methylation that contributes to tumorigenesis. Inflammation is associated with an increase in reactive oxygen species (ROS) that cause oxidative DNA damage, which has also been linked to epigenetic alterations. We previously demonstrated that in response to ROS, mismatch repair proteins MSH2 and MSH6 recruit epigenetic silencing proteins DNA methyltransferase 1 (DNMT1) and polycomb repressive complex 2 (PRC2) members to sites of DNA damage, resulting in transcriptional repression of tumor suppressor genes (TSGs). However, it was unclear what signal is unique to ROS that results in the chromatin binding of MSH2 and MSH6. Herein, we demonstrate that in response to hydrogen peroxide (H₂ O₂ ), JAK2 loc

SUBMITTER: Ding N 

PROVIDER: S-EPMC8504556 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature