Nucleotide excision repair affects the stability of long transcribed (CTG*CAG) tracts in an orientation-dependent manner in Escherichia coli.
AUTOR(ES)
Parniewski, P
RESUMO
The influence of nucleotide excision repair (NER), the principal in vivo repair system for DNA damages, was investigated in Escherichia coli with uvrA, uvrB and uvrAuvrB mutants with the triplet repeat sequences (TRS) involved in myotonic dystrophy, the fragile X syndrome and Friedreich's ataxia. (CTG*CAG)175was more stable when the (CTG) strand was transcribed than when the (CAG) strand was transcribed in the alternate orientation. A lack of the UvrA protein dramatically increases the instability of this TRS in vivo as compared with the stability of the same sequence in uvrB mutant, which produces an intact UvrA protein. We propose that transcription transiently dissociates the triplet repeat complementary strands enabling the non-transcribed strand to fold into a hairpin conformation which is then sufficiently stable that replication bypasses the hairpin to give large deletions. If the TRS was not transcribed, fewer deletions were observed. Alternatively, in the uvrA-mutant, the hairpins existing on the lagging strand will suffer bypass DNA synthesis to generate deleted molecules. Hence, NER, functionally similar in both prokaryotes and eukaryotes, is an important factor in the genetic instabilities of long transcribed TRS implicated in human hereditary neuro-logical diseases.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=148223Documentos Relacionados
- Orientation-dependent and sequence-specific expansions of CTG/CAG trinucleotide repeats in Saccharomyces cerevisiae
- Transcription increases the deletion frequency of long CTG.CAG triplet repeats from plasmids in Escherichia coli.
- Stability of a CTG/CAG trinucleotide repeat in yeast is dependent on its orientation in the genome.
- Orientation-dependent visibility of long thin objects in polarization-based microscopy.
- Transcription influences the types of deletion and expansion products in an orientation-dependent manner from GAC•GTC repeats