Proteomic analysis of mismatch repair-mediated alkylating agent-induced DNA damage response

Authors

Xi Chen, Wuhan University, China
Yong Zhao, Wuhan University, China
Guo-Min Li, University of KentuckyFollow
Lin Guo, Wuhan University, China

Abstract

BACKGROUND: Mediating DNA damage-induced apoptosis is an important genome-maintenance function of the mismatch repair (MMR) system. Defects in MMR not only cause carcinogenesis, but also render cancer cells highly resistant to chemotherapeutics, including alkylating agents. To understand the mechanisms of MMR-mediated apoptosis and MMR-deficiency-caused drug resistance, we analyze a model alkylating agent (N-methyl-N’-nitro-N-nitrosoguanidine, MNNG)-induced changes in protein phosphorylation and abundance in two cell lines, the MMR-proficient TK6 and its derivative MMR-deficient MT1.

RESULTS: Under an experimental condition that MNNG-induced apoptosis was only observed in MutSα-proficient (TK6), but not in MutSα-deficient (MT1) cells, quantitative analysis of the proteomic data revealed differential expression and phosphorylation of numerous individual proteins and clusters of protein kinase substrates, as well differential activation of response pathways/networks in MNNG-treated TK6 and MT1 cells. Many alterations in TK6 cells are in favor of turning on the apoptotic machinery, while many of those in MT1 cells are to promote cell proliferation and anti-apoptosis.

CONCLUSIONS: Our work provides novel molecular insights into the mechanism of MMR-mediated DNA damage-induced apoptosis.

Document Type

Article

Publication Date

9-19-2013

Notes/Citation Information

Published in Cell & Bioscience, v. 3, 37.

© 2013 Chen et al.; licensee BioMed Central Ltd.

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Digital Object Identifier (DOI)

http://dx.doi.org/10.1186/2045-3701-3-37

Repository Citation

Chen, Xi; Zhao, Yong; Li, Guo-Min; and Guo, Lin, "Proteomic analysis of mismatch repair-mediated alkylating agent-induced DNA damage response" (2013). Toxicology and Cancer Biology Faculty Publications. 10.
https://uknowledge.uky.edu/toxicology_facpub/10