Both hMutSα and hMutSß DNA mismatch repair complexes participate in 5-fluorouracil cytotoxicity.
Both hMutSα and hMutSß DNA mismatch repair complexes participate in 5-fluorouracil cytotoxicity.
复制标题
DOI：
10.1371/journal.pone.0028117
复制
发表时间：
2011
期刊：
影响因子：
3.7
通讯作者：
Carethers JM
中科院分区：
文献类型：
--
作者：
Tajima A;Iwaizumi M;Tseng-Rogenski S;Cabrera BL;Carethers JM
Patients with advanced microsatellite unstable colorectal cancers do not show a survival benefit from 5-fluorouracil (5-FU)-based chemotherapy. We and others have shown that the DNA mismatch repair (MMR) complex hMutSα binds 5-FU incorporated into DNA. Although hMutSß is known to interact with interstrand crosslinks (ICLs) induced by drugs such as cisplatin and psoralen, it has not been demonstrated to interact with 5-FU incorporated into DNA. Our aim was to examine if hMutSß plays a role in 5-FU recognition. We compared the normalized growth of 5-FU treated cells containing either or both mismatch repair complexes using MTT and clonogenic assays. We utilized oligonucleotides containing 5-FU and purified baculovirus-synthesized hMutSα and hMutSß in electromobility shift assays (EMSA) and further analyzed binding using surface plasmon resonance. MTT and clonogenic assays after 5-FU treatment demonstrated the most cytotoxicity in cells with both hMutSα and hMutSß, intermediate cytotoxicity in cells with hMutSα alone, and the least cytotoxicity in cells with hMutSß alone, hMutSß binds 5-FU-modified DNA, but its relative binding is less than the binding of 5-FU-modified DNA by hMutSα. Cytotoxicity induced by 5-FU is dependent on intact DNA MMR, with relative cell death correlating directly with hMutSα and/or hMutSß 5-FU binding ability (hMutSα>hMutSß). The MMR complexes provide a hierarchical chemosensitivity for 5-FU cell death, and may have implications for treatment of patients with certain MMR-deficient tumors.
登录
查看更多内容
影响因子：
29.4
作者：
Boland CR;Goel A
通讯作者：
Goel A
影响因子：
4.8
作者：
Meyers, M;Wagner, MW;Boothman, DA
通讯作者：
Boothman, DA
影响因子：
5.3
作者：
Zhang, NX;Lu, XY;Legerski, RJ
通讯作者：
Legerski, RJ
DOI：
10.1007/s11605-010-1340-6
发表时间：
2010-10
期刊：
Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract
影响因子：
--
作者：
Devaraj B;Lee A;Cabrera BL;Miyai K;Luo L;Ramamoorthy S;Keku T;Sandler RS;McGuire KL;Carethers JM
通讯作者：
Carethers JM
影响因子：
9.2
作者：
Habraken, Y;Sung, P;Prakash, S
通讯作者：
Prakash, S