Heterochromatinization associated with cell differentiation as a model to study DNA double strand break induction and repair in the context of higher-order chromatin structure

• Published in: Applied radiation and isotopes 2014-01, Vol.83, p.177-185
• Main Authors: Falk, Martin, Lukášová, Emilie, Štefančíková, Lenka, Baranová, Elena, Falková, Iva, Ježková, Lucie, Davídková, Marie, Bačíková, Alena, Vachelová, Jana, Michaelidesová, Anna, Kozubek, Stanislav
• Format: Article
• Language: English
• Subjects: Cell Differentiation; Cells, Cultured; Chromatin - chemistry; Chromatin sensitivity to DSB induction; DNA Damage; DNA double strand break (DSB) repair; DNA Repair; Heterochromatin; Higher-order chromatin structure; Humans; Immature and terminally differentiated granulocytes; In Situ Hybridization, Fluorescence; Protein Conformation; γH2AX/53BP1 repair foci
• ISSN: 0969-8043; 1872-9800
• DOI: 10.1016/j.apradiso.2013.01.029

Cell differentiation is associated with extensive gene silencing, heterochromatinization and potentially decreasing need for repairing DNA double-strand breaks (DSBs). Differentiation stages of blood cells thus represent an excellent model to study DSB induction, repair and misrepair in the context of changing higher-order chromatin structure. We show that immature granulocytes form γH2AX and 53BP1 foci, contrary to the mature cells; however, these foci colocalize only rarely and DSB repair is inefficient. Moreover, specific chromatin structure of granulocytes probably influences DSB induction. ► DSB repair is absent in mature granulocytes with condensed chromatin. ► Repair proteins and γH2AX appear in immature stages but rarely colocalize. ► γH2AX persist long times in these cells and DSB repair is inefficient. ► Even though, γH2AX foci “move” out of the dense chromatin. ► 53BP1 enters HP1β domains only after their decondensation.