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Nucleic Acids Research, 2001, Vol. 29, No. 16 3304-3310
© 2001 Oxford University Press

Suppression of gene amplification and chromosomal DNA integration by the DNA mismatch repair system

Ching-Tai Lin*, Yi Lisa Lyu1, Hai Xiao2, Wei-Hsin Lin and Jacqueline Whang-Peng

National Health Research Institute, Cancer Research Division, Cooperative Laboratory, Veterans General Hospital, 201 Shih-Pai Road, Sec. 2, Taipei 112, Taiwan, Republic of China, 1MCB, Harvard University, 7 Divinity Avenue, Cambridge, MA 02138, USA and 2Department of Pharmacology, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, NJ 08854, USA

Mismatch repair (MMR)-deficient cells are shown to produce >15-fold more methotrexate-resistant colonies than MMR normal cells. The increased resistance to methotrexate is primarily due to gene amplification since all the resistant clones contain double-minute chromosomes and increased copy numbers of the DHFR gene. In addition, integration of linearized or retroviral DNAs into chromosomes is also significantly elevated in MMR-deficient cells. These results suggest that in addition to microsatellite instability and homeologous recombination, MMR is also involved in suppression of other genome instabilities such as gene amplification and chromosomal DNA integration.

* To whom correspondence should be addressed. Tel: +886 2 28712121; Fax: +886 2 28733664; Email: linct{at}nhri.org.tw


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