Review of Mammalian DNA Repair and Translational Implications1
- Department of Pediatrics, Section of Hematology/Oncology, Herman B. Wells Center for Pediatric Research and Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana
Abstract
The area of mammalian DNA repair and its relationship to cancer and therapeutic approaches is rapidly growing, both through the studies of basic mechanisms and in the use of this knowledge for translational applications. We have attempted to briefly and succinctly cover the four pathways of mammalian DNA repair, which are: direct reversal, mismatch, nucleotide excision, and base excision repair. We have also tried to identify and reference results in the literature relating the various repair pathways to cellular resistance following chemotherapeutic treatments and to provide some potential direction whereby laboratory results may be applicable to clinical therapeutics, particularly for cancer treatments.
Footnotes
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Send reprint requests to: Mark R. Kelley, Ph.D., Department of Pediatrics (Hematology/Oncology), Herman B. Wells Center for Pediatric Research, 702 Barnhill Dr., Rm. 2600, Indianapolis, IN 46202. E-mail: mkelley{at}iupui.edu
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↵1 The authors were supported by National Institutes of Health/National Cancer Institute Program Project Grant PO1-CA75426 and by NIH Grants CA76643, ES07815, NS38506, Army CDMRP OC990085, and the Gynecologic Oncology Group (GOG) Ovarian Cancer Research Fund. We also apologize to all those investigators whose references we had to leave out due to the limitation of references allowed.
- Abbreviations:
- MMR
- mismatch repair
- BER
- base excision repair
- NER
- nucleotide excision repair
- MMS
- methyl methanesulfonate
- MGMT/AGT
- O6-methylguanine-DNA methyltransferase
- BCNU
- 1,3-bis(2-chloroethyl)-1-nitrosourea
- HNPCC
- hereditary nonpolyposis colon cancer
- XP
- xeroderma pigmentosum
- RPA
- replication protein A
- TFIIH
- transcription factor IIH (XPB, XPD, p62, p52, p44, p44)
- ERCC1
- excision repair cross-complementing 1
- FEN
- flap endonuclease
- PCNA
- proliferating cell nuclear antigen
- RFC
- replication factor C
- O6-meG
- O6-methylguanine
- XRCC1
- X-ray cross-species complementing 1
- 8-oxoG
- 7,8-dihydro-8-oxoguanine
- Fpg
- formamidopyrimidine glycosylase
- 3-meA
- 3-methyladenine
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- Received March 10, 2000.
- Accepted April 17, 2000.
- The American Society for Pharmacology and Experimental Therapeutics
