DNA topoisomerases as repair enzymes: Mechanism[s] of action and regulation by p53

• Autorzy: Larsen A. K. , Gobert C. , Gilbert C. , Markovits J. , Bojanowski K. , Skladanowski A.
• Języki publikacji: EN

Abstrakty

EN

DNA topoisomerases regulate the organization of DNA and are important targets for many clinically used antineoplastic agents. In addition, DNA topoisomerases modulate the cellular sensitivity toward a number of DNA damaging agents. Increased topoisomerase II activities were shown to contribute to the resistance of both nitrogen mustard- and cisplatin-resistant cells. Similarly, cells with decreased topoisomerase II levels show increased sensitivity to cisplatin, carmustine, mitomycin C and nitrogen mustard. Recent studies propose that topoisomerases may be involved in damage recognition and DNA repair at several different levels including: 1) the initial recognition of DNA lesions; 2) DNA recombination; and 3) regulation of DNA structure. The stress-activated oncogene suppressor protein p53 can modulate the activity of at least three different human topoisomerases, either directly by molecular associations or by transcriptional regulation. Since DNA topoisomerases have considerable recombinase activities, inappropriately activated topoisomerases in tumor cells lacking functional p53 may contribute to the genetic instability of these cells.

Słowa kluczowe

EN

chromatin; alkylating agent; man; damage recognition; DNA repair; nuclear structure; recombination; topoisomerase; DNA topoisomerase

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 1998
• Tom: 45
• Numer: 2
• Opis fizyczny: p.535-544,fig.

Twórcy

autor

Larsen A. K.

• Institut Gustave-Roussy PR2, Villejuif 94805, Cedex, France

autor

Gobert C.

autor

Gilbert C.

autor

Markovits J.

autor

Bojanowski K.

autor

Skladanowski A.

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