Toggle Main Menu Toggle Search

Open Access padlockePrints

Interactions of the DNA mismatch repair proteins MLH1 and MSH2 with c-MYC and MAX

Lookup NU author(s): Elizabeth Matheson, Dr Andrew Hall


Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


MSH2 and MLH1 have a central role in correcting mismatches in DNA occurring during DNA replication and have been implicated in the engagement of apoptosis induced by a number of cytotoxic anticancer agents. The function of MLH1 is not clearly defined, although it is required for mismatch repair (MMR) and engagement of apoptosis after certain types of DNA damage. In order to identify other partners of MLH1 that may be involved in signalling MMR or apoptosis, we used human MLH1 in yeast two-hybrid screens of normal human breast and ovarian cDNA libraries. As well as known partners of MLH1 such as PMS1, MLH3 and MBD4, we identified the carboxy terminus of the human c-MYC protooncogene as an interacting sequence. We demonstrate, both in vitro by yeast two-hybrid and GST-fusion pull-down experiments, as well as in vivo by coimmunoprecipitation from human tumour cell extracts, that MLH1 interacts with the c-MYC protein. We further demonstrate that the heterodimeric partner of c-MYC, MAX, interacts with a different MMR protein, MSH2, both in vitro and in vivo. Using an inducible c-MYC-ER(TM) fusion gene, we show that elevated c-MYC expression leads to an increased HGPRT mutation rate of Rat1 cells and an increase in the number of frameshift mutants at the HGPRT locus. The effect on HGPRT mutation rate is small (2-3-fold), but is consistent with deregulated c-MYC expression partially inhibiting MMR activity.

Publication metadata

Author(s): MacPartlin M, Homer E, Robinson H, McCormick CJ, Crouch DH, Durant ST, Matheson EC, Hall AG, Gillespie DAF, Brown R

Publication type: Article

Publication status: Published

Journal: Oncogene

Year: 2003

Volume: 22

Issue: 6

Pages: 819-825

ISSN (print): 0950-9232

ISSN (electronic): 1476-5594


DOI: 10.1038/sj.onc.1206252

PubMed id: 12584560


Altmetrics provided by Altmetric