Résumé
One characteristic of genomic plasticity is the presence of extrachromosomal
circular DNA (eccDNA). High levels of eccDNA are associated with
genomic instability, exposure to carcinogens and aging. We have
recently reported developmentally regulated formation of eccDNA
that occurs preferentially in pre-blastula Xenopus laevis embryos. Multimers of tandemly repeated
sequences were over-represented in the circle population while dispersed sequences
were not detected, indicating that circles were not formed at random
from any chromosomal sequence. Here we present detailed mechanistic studies
of eccDNA formation in a cell-free system derived from Xenopus egg
extracts. We show that naked chromosomal DNA from sperm or somatic tissues
serves as a substrate for direct tandem repeat circle formation.
Moreover, a recombinant bacterial tandem repeat can generate eccDNA
in the extract through a de novo mechanism which
is independent of DNA replication. These data suggest that the presence
of a high level of any direct tandem repeat can confer on DNA the
ability to be converted into circular multimers in the early embryo
irrespective of its sequence and that homologous recombination is
involved in this process.