%0 Journal Article
%T DNA Damage Changes Distribution Pattern and Levels of HP1 Protein Isoforms in the Nucleolus and Increases Phosphorylation of HP1¦Â-Ser88
%J Cells | An Open Access Journal from MDPI
%D 2019
%R https://doi.org/10.3390/cells8091097
%X The family of heterochromatin protein 1 (HP1) isoforms is essential for chromatin packaging, regulation of gene expression, and repair of damaged DNA. Here we document that ¦Ă-radiation reduced the number of HP1¦Á-positive foci, but not HP1¦Â and HP1¦Ă foci, located in the vicinity of the fibrillarin-positive region of the nucleolus. The additional analysis confirmed that ¦Ă-radiation has the ability to significantly decrease the level of HP1¦Á in rDNA promoter and rDNA encoding 28S rRNA. By mass spectrometry, we showed that treatment by ¦Ă-rays enhanced the HP1¦Â serine 88 phosphorylation (S88ph), but other analyzed modifications of HP1¦Â, including S161ph/Y163ph, S171ph, and S174ph, were not changed in cells exposed to ¦Ă-rays or treated by the HDAC inhibitor (HDACi). Interestingly, a combination of HDACi and ¦Ă-radiation increased the level of HP1¦Á and HP1¦Ă. The level of HP1¦Â remained identical before and after the HDACi/¦Ă-rays treatment, but HDACi strengthened HP1¦Â interaction with the KRAB-associated protein 1 (KAP1) protein. Conversely, HP1¦Ă did not interact with KAP1, although approximately 40% of HP1¦Ă foci co-localized with accumulated KAP1. Especially HP1¦Ă foci at the periphery of nucleoli were mostly absent of KAP1. Together, DNA damage changed the morphology, levels, and interaction properties of HP1 isoforms. Also, ¦Ă-irradiation-induced hyperphosphorylation of the HP1¦Â protein; thus, HP1¦Â-S88ph could be considered as an important marker of DNA damage. View Full-Tex
%U https://www.mdpi.com/2073-4409/8/9/1097