Menon Vijay, Povirk Lawrence
Goodwin Research Laboratories, Massey Cancer Center, Virginia Commonwealth University, 401 College Street, Room No. 380A, Richmond, VA, 23298-0035, USA.
Subcell Biochem. 2014;85:321-36. doi: 10.1007/978-94-017-9211-0_17.
p53 is a tumor suppressor protein that prevents oncogenic transformation and maintains genomic stability by blocking proliferation of cells harboring unrepaired or misrepaired DNA. A wide range of genotoxic stresses such as DNA damaging anti-cancer drugs and ionizing radiation promote nuclear accumulation of p53 and trigger its ability to activate or repress a number of downstream target genes involved in various signaling pathways. This cascade leads to the activation of multiple cell cycle checkpoints and subsequent cell cycle arrest, allowing the cells to either repair the DNA or undergo apoptosis, depending on the intensity of DNA damage. In addition, p53 has many transcription-independent functions, including modulatory roles in DNA repair and recombination. This chapter will focus on the role of p53 in regulating or influencing the repair of DNA double-strand breaks that mainly includes homologous recombination repair (HRR) and non-homologous end joining (NHEJ). Through this discussion, we will try to establish that p53 acts as an important linchpin between upstream DNA damage signaling cues and downstream cellular events that include repair, recombination, and apoptosis.
p53是一种肿瘤抑制蛋白，它通过阻止携带未修复或错配DNA的细胞增殖来防止致癌转化并维持基因组稳定性。多种基因毒性应激，如DNA损伤抗癌药物和电离辐射，会促进p53的核积累，并触发其激活或抑制参与各种信号通路的许多下游靶基因的能力。这一级联反应导致多个细胞周期检查点的激活和随后的细胞周期停滞，使细胞能够根据DNA损伤的强度修复DNA或发生凋亡。此外，p53具有许多不依赖转录的功能，包括在DNA修复和重组中的调节作用。本章将重点关注p53在调节或影响DNA双链断裂修复中的作用，这主要包括同源重组修复（HRR）和非同源末端连接（NHEJ）。通过本次讨论，我们将试图确定p53作为上游DNA损伤信号线索与下游细胞事件（包括修复、重组和凋亡）之间的重要关键环节。
