DNA Damage Changes Distribution Pattern and Levels of HP1 Protein Isoforms in the Nucleolus and Increases Phosphorylation of HP1?-Ser88.

ABSTRACT: 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 ?-radiation reduced the number of HP1?-positive foci, but not HP1? and HP1? foci, located in the vicinity of the fibrillarin-positive region of the nucleolus. The additional analysis confirmed that ?-radiation has the ability to significantly decrease the level of HP1? in rDNA promoter and rDNA encoding 28S rRNA. By mass spectrometry, we showed that treatment by ?-rays enhanced the HP1? serine 88 phosphorylation (S88ph), but other analyzed modifications of HP1?, including S161ph/Y163ph, S171ph, and S174ph, were not changed in cells exposed to ?-rays or treated by the HDAC inhibitor (HDACi). Interestingly, a combination of HDACi and ?-radiation increased the level of HP1? and HP1?. The level of HP1? remained identical before and after the HDACi/?-rays treatment, but HDACi strengthened HP1? interaction with the KRAB-associated protein 1 (KAP1) protein. Conversely, HP1? did not interact with KAP1, although approximately 40% of HP1? foci co-localized with accumulated KAP1. Especially HP1? 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, ?-irradiation-induced hyperphosphorylation of the HP1? protein; thus, HP1?-S88ph could be considered as an important marker of DNA damage.

SUBMITTER: Legartova S 

PROVIDER: S-EPMC6770535 | biostudies-literature | 2019 Sep

REPOSITORIES: biostudies-literature