Depletion of A-type lamins and Lap2α reduces 53BP1 accumulation at UV-induced DNA lesions and Lap2α protein is responsible for compactness of irradiated chromatin

0486721 - BFÚ 2018 RIV US eng J - Článek v odborném periodiku
Bártová, Eva - Legartová, Soňa - Krejčí, Jana - Řezníčková, Petra - Kovaříková, Alena - Suchánková, Jana - Fedr, Radek - Smirnov, E. - Hornáček, M. - Raška, I.
Depletion of A-type lamins and Lap2α reduces 53BP1 accumulation at UV-induced DNA lesions and Lap2α protein is responsible for compactness of irradiated chromatin.
Journal of Cellular Biochemistry. Roč. 2018, č. 2018 (2018). ISSN 0730-2312. E-ISSN 1097-4644
Grant CEP: GA ČR GBP302/12/G157; GA MŠMT 7F14369
Institucionální podpora: RVO:68081707
Klíčová slova: DAPI * DNA damage response * FLIM
Obor OECD: Cell biology
Impakt faktor: 3.448, rok: 2018

We studied how deficiency in lamins A/C and lamina-associated polypeptide α (Lap2α) affects DNA repair after irradiation. A-type lamins and Lap2α were not recruited to local DNA lesions and did not accumulate to γ-irradiation-induced foci (IRIF), as it is generally observed for well-known marker of DNA lesions, 53BP1 protein. At micro-irradiated chromatin of lmna double knockout (dn) and Lap2α dn cells, 53BP1 protein levels were reduced, compared to locally irradiated wild-type counterpart. Decreased levels of 53BP1 we also observed in whole populations of lmna dn and Lap2α dn cells, irradiated by UV light. We also studied distribution pattern of 53BP1 protein in a genome outside micro-irradiated region. In Lap2α deficient cells, identical fluorescence of mCherry-tagged 53BP1 protein was found at both microirradiated region and surrounding chromatin. However, a well marker of double strand breaks, γH2AX, was highly abundant in the lesion-surrounding genome of Lap2α deficient cells. Described changes, induced by irradiation in Lap2α dn cells, were not accompanied by cell cycle changes. In Lap2α dn cells, we additionally performed analysis by FLIM (Fluorescence Lifetime Imaging Microscopy) that showed different dynamic behavior of mCherry-tagged 53BP1 protein pools when it was compared with wild-type (w-t) fibroblasts.
Trvalý link: http://hdl.handle.net/11104/0281458