Participation of DNA repair in the response to 5-fluorouracil.

Participation of DNA repair in the response to 5-fluorouracil.
复制标题

DOI:
10.1007/s00018-008-8557-5
复制
发表时间:
2009-03
影响因子:
8
通讯作者:
Wilson, D. M., III
Wilson, D. M., III
中科院分区:
生物学1区
文献类型:
--
作者:
Wyatt, M. D.;Wilson, D. M., III

文献摘要

参考文献

被引文献

相似文献

抗代谢物5-氟尿嘧啶(5-FU)在临床上用于治疗实体瘤,包括结直肠癌和乳腺癌。5-FU的细胞内代谢物可通过抑制胸苷酸合成酶或通过掺入RNA和DNA(最终激活细胞凋亡的事件)发挥细胞毒性作用。在这篇综述中,我们涵盖了目前的数据牵连DNA修复过程中的细胞反应5-FU治疗。有证据表明碱基切除修复(BER)和错配修复(MMR)的作用。然而,机制的细节仍然无法解释,和其他途径还没有被彻底询问。同源重组是特别感兴趣的,因为它解决了未修复的DNA中间体没有正确处理的BER或MMR。此外,DNA修复途径和S期检查点信号传导之间的串扰尚未被检查。正在进行的努力旨在设计方法和试剂,(i)近似修复能力和(ii)介导DNA修复的战略调控,以提高目前抗癌治疗的疗效。
The anti-metabolite 5-fluorouracil (5-FU) is employed clinically to manage solid tumors including colorectal and breast cancer. Intracellular metabolites of 5-FU can exert cytotoxic effects via inhibition of thymidylate synthetase, or through incorporation into RNA and DNA, events that ultimately activate apoptosis. In this review, we cover the current data implicating DNA repair processes in cellular responsiveness to 5-FU treatment. Evidence points to roles for base excision repair (BER) and mismatch repair (MMR). However, mechanistic details remain unexplained, and other pathways have not been exhaustively interrogated. Homologous recombination is of particular interest, because it resolves unrepaired DNA intermediates not properly dealt with by BER or MMR. Furthermore, crosstalk among DNA repair pathways and S-phase checkpoint signaling has not been examined. Ongoing efforts aim to design approaches and reagents that (i) approximate repair capacity and (ii) mediate strategic regulation of DNA repair in order to improve the efficacy of current anti-cancer treatments.
DOI: 10.1073/pnas.2334585100
发表时间: 2003-12-09
影响因子: 11.1
作者:
Cortellino, S;Turner, D;Bellacosa, A
通讯作者: Bellacosa, A
DOI: 10.1093/carcin/bgh347
发表时间: 2005-03-01
期刊: CARCINOGENESIS
影响因子: 4.7
作者:
Andersen, S;Heine, T;Nilsen, H
通讯作者: Nilsen, H
DOI: 10.1016/j.bcp.2008.05.019
发表时间: 2008-09-15
影响因子: 5.8
作者:
Berger, Sondra H.;Pittman, Douglas L.;Wyatt, Michael D.
通讯作者: Wyatt, Michael D.
DOI: 10.1016/0027-5107(88)90086-3
发表时间: 1988-07-01
期刊: MUTATION RESEARCH
影响因子: --
作者:
AYUSAWA, D;ARAI, H;SENO, T
通讯作者: SENO, T
DOI: 10.1053/j.gastro.2007.09.003
发表时间: 2007-12-01
期刊: GASTROENTEROLOGY
影响因子: 29.4
作者:
Fischer, Franziska;Baerenfaller, Katja;Jiricny, Josef
通讯作者: Jiricny, Josef