Identification of a Saccharomyces cerevisiae gene that is required for G1 arrest in response to the lipid oxidation product linoleic acid hydroperoxide
N. Alic et al., Identification of a Saccharomyces cerevisiae gene that is required for G1 arrest in response to the lipid oxidation product linoleic acid hydroperoxide, MOL BIOL CE, 12(6), 2001, pp. 1801-1810
Reactive oxygen species cause damage to all of the major cellular constitue
nts, including peroxidation. of lipids. Previous studies have revealed that
oxidative stress, including exposure to oxidation products, affects the pr
ogression of cells through the cell division cycle. This study examined the
effect of linoleic acid hydroperoxide, a lipid peroxidation product, on th
e yeast cell cycle. Treatment with this peroxide led to accumulation of unb
udded cells in asynchronous populations, together with a budding and replic
ation delay in synchronous ones. This observed modulation of GI progression
could be distinguished from the lethal effects of the treatment and may ha
ve been due to a checkpoint mechanism, analogous to that known to be involv
ed in effecting cell cycle arrest in response to DNA damage. By examining s
everal mutants sensitive to linoleic acid hydroperoxide, the YNL099c open r
eading frame was found to be required for the arrest. This gene (designated
OCA1) encodes a putative protein tyrosine phosphatase of previously unknow
n function. Cells lacking OCA1 did not accumulate in GI on treatment with l
inoleic acid hydroperoxide, nor did they show a budding, replication, or St
art delay in synchronous cultures. Although not essential for adaptation or
immediate cellular survival, OCA1 was required for growth in the presence
of linoleic acid hydroperoxide, thus indicating that it may function in lin
king growth, stress responses, and the cell cycle. Identification of OCA1 e
stablishes cell cycle arrest as an actively regulated response to oxidative
stress and will enable further elucidation of oxidative stress-responsive
signaling pathways in yeast.