Mechanisms of genotoxin-induced transcription and hypermutation in p53.
Mechanisms of genotoxin-induced transcription and hypermutation in p53.
复制标题
p53中基因毒素诱导的转录和超名的机制。
DOI：
10.1186/1475-2867-6-27
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发表时间：
2006-12-01
影响因子：
5.8
通讯作者：
Wei, Ping
中科院分区：
文献类型：
--
作者：
Wright, Barbara;Reimers, Jacqueline;Schmidt, Karen;Burkala, Evan;Davis, Nick;Wei, Ping
It is widely assumed that genotoxin-induced damage (e.g., G-to-T transversions) to the tumor suppressor gene, p53, is a direct cause of cancer. However, genotoxins also induce the stress response, which upregulates p53 transcription and the formation of secondary structures from ssDNA. Since unpaired bases are thermodynamically unstable and intrinsically mutable, increased transcription could be the cause of hypermutation, and thus cancer. Support for this hypothesis has been obtained by analyzing 6662 mutations in all types of cancer compared to lung and colon cancers, using the p53 mutation database. The data suggest that genotoxins have two independent effects: first, they induce p53 transcription, which increases the number of mutable bases that determine the incidence of cancer. Second, genotoxins may alter the fate, or ultimate mutation of a mutable base, for example, by causing more of the available mutable Gs to mutate to T, leaving fewer to mutate to A. Such effects on the fate of mutable bases have no impact on the incidence of cancer, as both types of mutations lead to cancer.
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影响因子：
64.5
作者：
KASTAN, MB;ZHAN, QM;FORNACE, AJ
通讯作者：
FORNACE, AJ
影响因子：
56.9
作者：
HOLLSTEIN, M;SIDRANSKY, D;HARRIS, CC
通讯作者：
HARRIS, CC
影响因子：
56.9
作者：
BAKER, SJ;MARKOWITZ, S;VOGELSTEIN, B
通讯作者：
VOGELSTEIN, B
影响因子：
4.4
作者：
Bachl, J;Carlson, C;Olsson, C
通讯作者：
Olsson, C
影响因子：
8
作者：
Amundson, SA;Do, KT;Fornace, AJ
通讯作者：
Fornace, AJ