p53的C末端结构域催化DNA复性以及完整单链DNA之间退火的链交换，并通过双喹啉霉素对受损DNA的优先识别，从双链体形成中消除受损单链DNA。

The C-terminal domain of p53 catalyzes DNA-renaturation and strand exchange toward annealing between intact ssDNAs and toward eliminating damaged ssDNA from duplex formation through preferential recognition of damaged DNA by a duocarmycin.

作者信息

Yokote H, Nishio K, Arioka H, Kurokawa H, Fukuoka K, Fukumoto H, Ishida T, Terada T, Itakura T, Saijo N

机构信息

Pharmacology Division, National Cancer Center Research Institute, Tokyo, Japan.

出版信息

Mutat Res. 1998 Dec 14;409(3):147-62. doi: 10.1016/s0921-8777(98)00052-4.

DOI:10.1016/s0921-8777(98)00052-4

PMID:9875290

Abstract

The C-terminal domain of p53 may bind single-stranded (ss) DNA ends and catalyze renaturation of ss complementary DNA molecules, suggesting a possible direct role for p53 in DNA repair (Proc. Natl. Acad. Sci. USA, 92, 9455-9459, 1995). We found that DU-86, a duocarmycin derivative which alkylates DNA, bound ssDNA and enhanced the DNA binding activity of the p53 C-terminus. DU-86 weakened p53-mediated catalysis of complementary ssDNA renaturation. p53 C-terminus catalyzed DNA strand transfer toward annealing between intact ssDNAs and toward eliminating DU-86-damaged ssDNA from duplex formation. These results suggest that p53, via the C-terminal domain, may play a direct role in DNA repair by preferential recognization and elimination of damaged DNA.

摘要

p53的C末端结构域可能结合单链（ss）DNA末端并催化ss互补DNA分子的复性，这表明p53在DNA修复中可能具有直接作用（《美国国家科学院院刊》，92，9455 - 9459，1995）。我们发现，DU - 86，一种使DNA烷基化的双环霉素衍生物，能结合ssDNA并增强p53 C末端的DNA结合活性。DU - 86削弱了p53介导的互补ssDNA复性催化作用。p53 C末端催化DNA链转移，使其在完整的ssDNA之间退火，并在双链形成过程中消除DU - 86损伤的ssDNA。这些结果表明，p53可能通过C末端结构域，通过优先识别和消除受损DNA在DNA修复中发挥直接作用。