A model for the involvement of Okazaki fragments maturation in the expansion of short tandem repeats.
We propose a model for the expansion of short tandem repeats (ESTR), a phenomenon which has been found to occur in human DNA and is associated with a dozen of neuromuscular diseases. The model is based mainly on theoretical considerations and recovers experimental data from the literature; it also finds support in preliminary results obtained by us in multiprimed polymerase chain reactions designed to assess the effects of a downstream primer on the fidelity of the elongation of an upstream one. The model links the occurrence of the ESTR to a defective maturation of the Okazaki fragments (OF), and in particular to an improper processing of their 3' termini. This may occur when the last OF approaches the 5' terminus of the previous one in a susceptible region of the template. It is postulated here that when a growing OF has progressed past the priming region and its main portion has been synthesized, upon approaching its conclusion, the final elongation may take place in a region of the template where certain triplets are repeated: in that case a series of aberrations on the elongation mechanism may occur. These aberrations could involve (a) the displacement of the 5' terminus of the penultimate, properly matured OF, enacted by the incoming 3' terminus of the last OF, (b) the switch of the latter to the displaced strand of the former as template, (c) the fold-back on itself of the growing 3' terminus of the last OF, (d) its assumption of an unusual structure because of the repetition, and (e) some impairment of its removal by structure-specific exo-endonuclease(s). Derangements of this last part of the process may trigger the ESTR.
Bellizzi
D
D
University of Calabria, Cosenza, Italy.
Losso
M A
MA
Sgaramella
V
V
D001483:Base Sequence; D004247:DNA / Q000235:genetics / Q000378:metabolism*; D004260:DNA Repair; D004261:DNA Replication; D008957:Models, Genetic; D011995:Recombination, Genetic; D020080:Tandem Repeat Sequences / Q000235:genetics*; D013698:Templates, Genetic
C022262:Okazaki fragments; D004247:DNA