Hypothesis: some mutagens directly alter specific chromosomal proteins (DNA topoisomerase II and peripheral proteins) to produce chromosome stickiness, which causes chromosome aberrations.
Recent biochemical and molecular biological data on the composition and structure of the chromosome and the nucleus, combined with observations on the chromosomes of mutant yeast cells and grasshopper neuroblasts, offer new perspectives on mutagen-induced chromosome stickiness and its relation to chromosome breakage. A hypothesis consistent with these data states that chromosome stickiness (i) results from changes in specific non-histone proteins (topoisomerase II and the peripheral proteins) that are integral components of the chromosome and whose function is necessary for separation and segregation of chromatids, the changes being caused either by mutation in structural genes for the proteins (heritable stickiness) or by direct action of mutagens on the proteins (induced stickiness); (ii) occurs in various degrees (slight, moderate, severe, extreme) that are determined by the number of target protein molecules affected, a certain number (threshold) of affected molecules at a given site on a chromosome being required to resist the forces of anaphase movement in order to produce microscopically detectable stickiness; (iii) results from molecular events that can occur at several phases of the cell cycle (including interphase), but can only be recognized at prometaphase, metaphase and anaphase; and (iv) causes chromosome aberrations by the physical stretching and breaking of chromatids at the sticky sites; hence the breakage resulting from stickiness is a secondary effect that requires anaphase movement, in contrast to breakage resulting from direct action of mutagens on DNA.
Gaulden
M E
ME
Radiology Department, University of Texas Health Science Center, Dallas, TX 75235.
D000818:Animals; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D002869:Chromosome Aberrations; D002875:Chromosomes / Q000187:drug effects / Q000648:ultrastructure*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism*; D008957:Models, Genetic; D009153:Mutagens / Q000633:toxicity*; D009154:Mutation
D002868:Chromosomal Proteins, Non-Histone; D009153:Mutagens; D004250:DNA Topoisomerases, Type II