Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-34236
Stojic, L; Cejka, P; Jiricny, J (2005). High doses of SN1 type methylating agents activate DNA damage signaling cascades that are largely independent of mismatch repair. Cell Cycle, 4(3):473-477.
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Methylating agents of the SN1 type represent an important class of cancer chemotherapeutics. Efficient killing by clinically-relevant doses of these agents requires cell division and low levels or absence of the repair enzyme methylguanine methyl transferase (MGMT). The process requires also an active mismatch repair (MMR) system, as treatment of cells with the prototypic methylating agent N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) could be shown to trigger a delayed cell cycle arrest, which was absolutely MMR-dependent. We now show that DNA damage signaling activated by high doses of MNNG is very rapid and largely MMR-independent. However, the MMR system still contributes towards cell killing, as MMR deficiency favors the long-term survival of the cells, albeit to a substantially smaller extent than when low MNNG concentrations are deployed.
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|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||04 Faculty of Medicine > Institute of Molecular Cancer Research
07 Faculty of Science > Institute of Molecular Cancer Research
|DDC:||570 Life sciences; biology|
|Deposited On:||09 Jul 2010 10:38|
|Last Modified:||02 Dec 2013 20:33|
|Free access at:||Publisher DOI. An embargo period may apply.|
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