Deficiency in homologous recombination is associated with changes in cell cycling and morphology in Saccharomyces cerevisiae.
Exp Cell Res
; 430(1): 113701, 2023 09 01.
Article
en En
| MEDLINE
| ID: mdl-37393982
ABSTRACT
Exposure of eukaryotic cells to ionizing radiation or clastogenic chemicals leads to formation of DNA double-strand breaks (DSBs). These lesions are also generated internally by chemicals and enzymes, in the absence of exogenous agents, though the sources and consequences of such endogenously generated DSBs remain poorly understood. In the current study, we have investigated the impact of reduced recombinational repair of endogenous DSBs on stress responses, cell morphology and other physical properties of S. cerevisiae (budding yeast) cells. Use of phase contrast and DAPI-based fluorescence microscopy combined with FACS analysis confirmed that recombination-deficient rad52 cell cultures exhibit chronically high levels of G2 phase cells. Cell cycle phase transit times during G1, S and M were similar in WT and rad52 cells, but the length of G2 phase was increased by three-fold in the mutants. rad52 cells were larger than WT in all phases of the cycle and displayed other quantifiable changes in physical characteristics. The high G2 cell phenotype was abolished when DNA damage checkpoint genes, but not spindle assembly checkpoint genes, were co-inactivated with RAD52. Several other RAD52 group mutants (rad51, rad54, rad55, rad57 and rad59) also exhibited the high G2 cell phenotype. The results indicate that recombination deficiency leads to accumulation of unrepaired DSBs during normal mitotic growth that activate a major stress response and produce distinct changes in cellular physiology and morphology.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Saccharomyces cerevisiae
/
Proteínas de Saccharomyces cerevisiae
Tipo de estudio:
Risk_factors_studies
Idioma:
En
Revista:
Exp Cell Res
Año:
2023
Tipo del documento:
Article
País de afiliación:
Estados Unidos