|
Kasper Astrup Eriksen
Localization of DNA damage by current exchanging
repair enzymes: effects of cooperativity on detection
time
Theoretical Biology and Medical Modelling 2,
15 (2005)
Abstract
Background: How DNA repair enzymes find the
relatively rare sites of damage is not known in great
detail. Recent experiments and molecular data suggest that
individual repair enzymes do not work independently of each
other, but interact with each other through charges
exchanged along the DNA. A damaged site in the DNA hinders
this exchange. The hypothesis is that the charge exchange
quickly liberates the repair enzymes from error-free
stretches of DNA. In this way, the sites of damage are
located more quickly but how much more quickly is not
known, nor is it known whether the charge exchange
mechanism has other observable consequences.
Results: Here the size of the speed-up gained from
this charge exchange mechanism is calculated and the
characteristic length and time scales are identified. In
particular, for Escherichia coli, I estimate the speed-up
is 50000/N, where N is the number of repair enzymes
participating in the charge exchange mechanism. Even though
N is not exactly known, a speed-up of order 10 is not
entirely unreasonable. Furthermore, upon over expression of
all the repair enzymes, the location time only varies as
N-1/2 and not as 1/N.
Conclusion: The revolutionary hypothesis that DNA
repair enzymes use charge exchange along DNA to locate
damaged sites more efficiently is actually sound from a
purely theoretical point of view. Furthermore, the
predicted collective behavior of the location time is
important in assessing the impact of stress-ful and
radioactive environments on individual cell mutation
rates.
LU TP 03-49
|