Also, H2A.Z exchange at DSB sites occurs in cooperation with the ATPase function of P400. Among histones, a fundamental marker of double-strand breaks (DSBs) is the phosphorylation of histone H2AX (γH2AX). This process is accompanied by changes in H4 acetylation. observed that histone H4 terminal tails recruit proteins involved in DNA damage response (DDR), including 53BP1, an important factor of the non-homologous end joining (NHEJ) mechanism. showed that H3K9 acetylation prevents H3K9 methylation, thereby inhibiting H3K9me2/3-dependent DNA repair processes. For instance, we recently observed HDAC1-dependent deacetylation of histone H3 lysine 9 (H3K9) in experimentally induced DNA lesions. Information about the function of ac4C RNA in the DNA repair process has not been published yet, but levels of histone acetylation are known to change when chromatin is damaged. N4-acetylcytidine (ac4C), a highly conserved RNA nucleobase, also contributes to the regulation of mRNA stability and efficiency of translation. In general, acetylation is a well-described cellular mechanism that regulates gene expression, especially in relation to histones. Alternatively, RNA modifications, including ac4C, could be direct markers of damaged RNAs. Ac4C RNA likely causes de-condensation of chromatin in the vicinity of DNA lesions, making it accessible for other DNA repair factors involved in the DNA damage response. Our data imply that the acetylation of N4-cytidine, especially in small RNAs, has an important role in mediating DNA damage repair. In addition, we observed that the PARP inhibitor, olaparib, prevents the recruitment of ac4C RNA to damaged chromatin. This process was not dependent on the G1, S, and G2 cell cycle phases. However, RNA cytidine acetyltransferase NAT10 did not accumulate to damaged sites, and NAT10 depletion did not affect the pronounced recruitment of ac4C RNA to DNA lesions. Ac4C RNA appears in the damaged genome from 2 to 45 min after microirradiation. Here, we observe a high level of ac4C RNA at DNA lesions in interphase cells and irradiated cells in telophase. For instance, the regulatory role of acetylation on N4-cytidine (ac4C) in RNA can be explored not only in terms of RNA stability and mRNA translation but also in DNA repair. RNA modifications have been known for many years, but their function has not been fully elucidated yet.
0 Comments
Leave a Reply. |
AuthorWrite something about yourself. No need to be fancy, just an overview. ArchivesCategories |