Regulation of homologous recombinational repair by lamin B1 in radiation-induced DNA damage

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Ning-Ang LiuSatoshi Tashiro

Abstract

DNA double-strand breaks (DSBs) are the major lethal lesion induced by ionizing radiation (IR). RAD51-dependent homologous recombination (HR) is one of the most important pathways in DSB repair and genome integrity maintenance. However, the mechanism of HR regulation by RAD51 remains unclear. To understand the mechanism of RAD51-dependent HR, we searched for interacting partners of RAD51 by a proteomics analysis and identified lamin B1 in human cells. Lamins are nuclear lamina proteins that play important roles in the structural organization of the nucleus and the regulation of chromosome functions. Immunoblotting analyses revealed that siRNA-mediated lamin B1 depletion repressed the DNA damage-dependent increase of RAD51 after IR. The repression was abolished by the proteasome inhibitor MG132, suggesting that lamin B1 stabilizes RAD51 by preventing proteasome-mediated degradation in cells with IR-induced DNA damage. We also showed that lamin B1 depletion repressed RAD51 focus formation and decreased the survival rates after IR. On the basis of these results, we propose that lamin B1 promotes DSB repair and cell survival by maintaining the RAD51 protein levels for HR upon DSB induction after IR.

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Citations

Mar 21, 2018·Experimental Biology and Medicine·Muriel W Lambert
Feb 17, 2018·Connective Tissue Research·Jian ZhangGuangming Zhou
May 24, 2019·Journal of Biochemistry·Lin ShiSatoshi Tashiro
Oct 5, 2019·Experimental Biology and Medicine·Muriel W Lambert
Jun 27, 2019·Cellular & Molecular Biology Letters·Sichuang TanSipin Tan
May 6, 2020·FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology·Hua QianXiaoguang Li
Dec 10, 2020·Médecine sciences : M/S·Paula FontanillaPascale Bertrand
Feb 4, 2021·Nucleic Acids Research·Laura A Murray-NergerIleana M Cristea
Dec 10, 2020·International Journal of Molecular Sciences·Xunwen XueNing-Ang Liu
May 1, 2021·Genes·Simon WillaumePascale Bertrand
Aug 29, 2021·Science Advances·Laure EtourneaudPascale Bertrand

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