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DNA damage and cell killing cause and effect?
Author(s) -
Elkind Mortimer M.
Publication year - 1985
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(19851115)56:10<2351::aid-cncr2820561002>3.0.co;2-h
Subject(s) - replisome , replicon , dna , dna damage , dna replication , biology , replication protein a , dna synthesis , microbiology and biotechnology , eukaryotic dna replication , genetics , plasmid , gene , dna binding protein , transcription factor
The evidence supporting a cause and effect relationship between DNA damage and cell killing is examined in the light of what is currently known about the organization and replication of genomic DNA in eukaryotic cells and the radioenergetics of DNA breakage. A large disparity is identified between characteristic doses for cell killing and for the production of DNA lesions ( i.e. , single‐ or double‐strand breaks). In contrast, the sensitive phase of the inhibition of DNA synthesis has a dependence on dose quantitatively similar to that of cell killing. A model is developed in which single‐ and double‐strand breaks are associated with the inhibition of replicon initiation, whereas only double‐strand breaks are primarily responsible for strand elongation. Furthermore, the model points to the replisome and the region of replicated DNA just downstream from the fork as the locus of radiation action.