Rp. Bowater et al., TRANSCRIPTION INCREASES THE DELETION FREQUENCY OF LONG CTG-CENTER-DOT-CAG TRIPLET REPEATS FROM PLASMIDS IN ESCHERICHIA-COLI, Nucleic acids research, 25(14), 1997, pp. 2861-2868
Induction of transcription into long CTG.CAG repeats contained on plas
mids in Escherichia coli is shown to increase the frequency of deletio
ns within the repeat sequences, This elevated genetic instability was
detected because active transcription into the triplet repeat influenc
ed the growth transitions of the host cell, allowing advantageous grow
th for cells harboring plasmids with deleted repeat sequences, The var
iety of deletion products observed in separate cultures suggests that
transcription altered the metabolism of the DNA in a manner that produ
ced random length changes in the repeat sequence, For cultures contain
ing plasmids without active transcription into the triplet repeat, or
those maintained in exponential growth, deletions occurred within the
repeat at a lower frequency (5-20-fold lower), In these incubations th
e extent of deletions was proportional to the number of cell divisions
and many repeat lengths were observed within each culture, suggesting
that the decrease in average repeat length at long incubation times w
as due to multiple small deletions, These observations show that delet
ions within long CTG.CAG repeats contained on plasmids in E. coli occu
r via more than one pathway and their level of genetic instability is
altered by the enzymatic processes occurring upon the DNA.