Ultra-violet light induced changes in DNA dynamics may enhance TT-dimer recognition.
Short-wave ultra-violet light promotes the formation of DNA dimers between adjacent thymine bases, and if unrepaired these dimers may induce skin cancer. Living cells have a very robust repair system capable of repairing hundreds of lesions every day. Although many of the details of the dimer repair mechanism are known, it is still a mystery how the dimers are recognized. Because the dimers are hidden from repair proteins diffusing in the cell nucleus, it has been surmised that dimer recognition is indirect. In this paper, a new recognition signal is suggested by a theory of the dimer-induced large amplitude, prolonged oscillations in the motion of the two strands in double-stranded DNA molecules. These large amplitude oscillations of the two DNA strands, localized around the dimer will unveil the dimer allowing the repair proteins to bind to the dimer site. The temperature dependence of the recognition rate is correlated with the inter-strand fluctuations and must decrease with decreasing temperature according to the findings in this paper. Moreover the probability for finding a large opening is localized to the dimer neighbourhood and these large openings may play an important role in dimer-repair protein biochemistry.
Blagoev
K B
KB
Theoretical Division, Los Alamos National Laboratory, NM 87545, USA. krastan@speedymail.org
Alexandrov
B S
BS
Goodwin
E H
EH
Bishop
A R
AR
D004247:DNA / Q000737:chemistry / Q000378:metabolism / Q000528:radiation effects; D004249:DNA Damage; D004260:DNA Repair; D006801:Humans; D066298:In Vitro Techniques; D008954:Models, Biological; D009010:Monte Carlo Method; D011740:Pyrimidine Dimers / Q000378:metabolism* / Q000528:radiation effects*; D014466:Ultraviolet Rays / Q000009:adverse effects
D011740:Pyrimidine Dimers; D004247:DNA