4.7 Article

Timing of Chromosome DNA Integration throughout the Yeast Cell Cycle

Journal

BIOMOLECULES
Volume 13, Issue 4, Pages -

Publisher

MDPI
DOI: 10.3390/biom13040614

Keywords

BIT; cell cycle; DNA integration; Pol32; yeast

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This study investigates the cell uptake and genomic integration of exogenous linear DNA in the model organism Saccharomyces cerevisiae throughout the cell cycle. The researchers found that transformability increases in S phase regardless of sequence homologies, and the efficiency of chromosomal integration depends on the genomic targets during a specific phase. The Pol32 polymerase was found to control a specific translocation between chromosomes XV and VIII during DNA synthesis. The cell-cycle dependent regulation of DNA repair pathways under stress and the increase of ROS levels following translocation events were also discovered.
The dynamic mechanism of cell uptake and genomic integration of exogenous linear DNA still has to be completely clarified, especially within each phase of the cell cycle. We present a study of integration events of double-stranded linear DNA molecules harboring at their ends sequence homologies to the host's genome, all throughout the cell cycle of the model organism Saccharomyces cerevisiae, comparing the efficiency of chromosomal integration of two types of DNA cassettes tailored for site-specific integration and bridge-induced translocation. Transformability increases in S phase regardless of the sequence homologies, while the efficiency of chromosomal integration during a specific cycle phase depends upon the genomic targets. Moreover, the frequency of a specific translocation between chromosomes XV and VIII strongly increased during DNA synthesis under the control of Pol32 polymerase. Finally, in the null POL32 double mutant, different pathways drove the integration in the various phases of the cell cycle and bridge-induced translocation was possible outside the S phase even without Pol32. The discovery of this cell-cycle dependent regulation of specific pathways of DNA integration, associated with an increase of ROS levels following translocation events, is a further demonstration of a sensing ability of the yeast cell in determining a cell-cycle-related choice of DNA repair pathways under stress.

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