Excision repair of DNA

Figure 36-23. Base excision-repair of DNA. The enzyme uracil DNA glycosylase removes the uracil created by spontaneous deamination of cytosine in the DNA. An endonuclease cuts the backbone near the defect then, after an endonuclease removes a few bases, the defect is filled in by the action of a repair polymerase and the strand is rejoined by a ligase. (Courtesy of B Alberts.)...

This work provides important evidence for elucidating the cytotoxic effect of the ruthenium-arene complexes and the influence of the arene thereon, for instance with respect to excision repair of DNA lesions and DNA destabilization. It also established two different classes of Ru(II) arene anticancer drugs, i.e. those bearing an arene that has the possibility to intercalate and those that do not. This distinction is important as we will see further differences in DNA binding interactions for these two classes (vide infra). 

Comparison between DNA repair and phospholipid repair The processes that can lead to DNA damage and the type of damage are described in Chapter 9 and Appendix 9.6. The repair processes involve removal of the specific nucleotide(s) by an exonuclease and replacement of the nucleotide by a DNA polymerase. Since the strand must be broken to remove the damage (by an endonuclease) these parts of the strand must be repaired by a ligase. The process is known as excision-repair. Of interest, there is a degree of similarity between the removal of damaged polyunsaturated fatty acids from phospholipids in membranes and replacement with a new fatty acid by two enzymes, a deacylase and an acyltransferase (see above and Chapter 11), and excision-repair of DNA. 

Cleaver, J.E. (1977). Methods for the study of excision repair of DNA damaged by physical and chemical mutagens, page 19 in Handbook on Mutagenicity Tkst Procedures, KiLBEY, B.J., LEGATOR, M., NICHOLS, W., AND Ramel, C., Eds. (Elsevier, Amsterdam). 

Krokan HE, Standal RSG (1997) DNA glycosylases in the base excision repair of DNA. Biochem J 325 1-16... 

Cleaver, J.E. Methods for studying excision repair of DNA damaged by physical and chemical mutagens, pp. 19-48. In B.J. Kilbey, M. Legator, W. Nichols, and C. Ramel, Eds. Handbook of Mutagenicity Test Procedures. Amsterdam Elsevier/North Holland, 1977. 

What enzymes are common to the processes of replication of DNA and excision repair of DNA damage in E. colil... 

Araujo, S.J., Tirode, F., Coin, F., Pospiech, H., Syvaoja, J.E., Stucki, M., Hubscher, U., Egly, J.M., and Wood, R.D. (2000) Nucleotide excision repair of DNA with recombinant human proteins definition of the minimal set of factors, active forms of TFIIH, and modulation by CAK. Genes Dev., 14, 349-359. 

Although correlations have been established in some cases between the extent of drug-DNA interaction and cytotoxicity, the relationship between excision repair of DNA damage and toxicity is not always clear. 

Batty, D., and R. Wood. 2000. Damage recognition in nucleotide excision repair of DNA. Gene 241 193-204. 

Wang, Z., Wu, X., and Friedberg, E. C. (1991). Nucleotide excision repair of DNA by human cell extracts is suppressed in reconstituted nucleosomes. / Biol. Chem. 266, 22472-22478. 

Rubbi CP, Milner J. p53 is a chromatin accessibility factor for nucleotide excision repair of DNA damage. EMBO J 2003 22 975-986. 

Cleaver JE, Bodell WJ, Borek C, Morgan WF, Schwartz JL (1983) Poly(ADP-ribose) spectators or participant in excision repair of DNA damage. In Miwa M, Hayaishi O, Shall S, Smulson M, Sugimura T (eds) ADP-ribosylation, DNA repair and cancer. VNU Sci Press, Utrecht, p 195... 

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