tailieunhanh - Báo cáo khoa học: Apoptosis and autophagy: Regulation of apoptosis by DNA damage signalling – roles of p53, p73 and HIPK2

Genomic stability is constantly threatened by DNA damage, caused by numerous environmental and intrinsic sources, including radiation, chemi-cals and oncogene expression. Consequently, cells have evolved a sophisti-cated signal transduction network to sense DNA damage and to mount an appropriate DNA damage response. | MINIREVIEW Apoptosis and autophagy Regulation of apoptosis by DNA damage signalling - roles of p53 p73 and HIPK2 Nadja Bitomsky and Thomas G. Hofmann German Cancer Research Center DKFZ Cellular Senescence Group DKFZ-ZMBH Alliance Heidelberg Germany Keywords apoptosis ataxia-telangiectasia mutated ATM ataxia-telangiectasia mutated and Rad3-related ATR DNA damage homeodomain-interacting protein kinase 2 HIPK2 nuclear bodies p53 p73 promyelocytic leukaemia PML Correspondence T. G. Hofmann German Cancer Research Center Cellular Senescence Group A210 DKFZ-ZMBH Alliance Im Neuenheimer Feld 242 69120 Heidelberg Germany Fax 49 0 6221 424902 Tel 49 0 6221 424631 E-mail Received 13 March 2009 revised 14 August 2009 accepted 27 August 2009 doi Genomic stability is constantly threatened by DNA damage caused by numerous environmental and intrinsic sources including radiation chemicals and oncogene expression. Consequently cells have evolved a sophisticated signal transduction network to sense DNA damage and to mount an appropriate DNA damage response. Dysregulation of the DNA damage response leads to genomic instability and cancer. Dependent on the cellular background and extent of DNA damage the DNA damage response triggers cell cycle arrest and DNA repair or in the case of irreparable damage inactivation of the cells by senescence or apoptosis. In this minireview we concentrate on the apoptotic response to DNA damage and signalling pathways linked to the cell nucleus and nuclear bodies with a particular focus on the molecular players p53 and p73 and on the DNA damage-activated kinase homeodomain-interacting protein kinase 2 HIPK2 . Introduction Protection of the genome and maintenance of genomic integrity following genotoxic stress is a crucial step in counteracting tumorigenesis. Eukaryotic organisms from yeasts to humans have developed efficient molecular mechanisms to sense different types of DNA damage. These different .