In the mitotic cell cycle of the yeast Saccharomyces cerevisiae, the sister
chromatid is preferred over the homologous chromosome (non-sister chromati
d) as a substrate for DNA double-strand break repair. However, no genes hav
e yet been shown to be preferentially involved in sister chromatid-mediated
repair. We developed a novel method to identify genes that are required fo
r repair by the sister chromatid, using a haploid strain that can embark on
meiosis, We show that the recombinational repair gene RAD54 is required pr
imarily for sister chromatid-based repair, whereas TID1, a yeast RAD54 homo
logue, and the meiotic gene DMC1, are dispensable for this type of repair.
Our observations suggest that the sister chromatid repair pathway, which in
volves RAD54, and the homologous chromosome repair pathway, which involves
DMC1, can substitute for one another under some circumstances. Deletion of
RAD54 in S.cerevisiae results in a phenotype similar to that found in mamma
lian cells, namely impaired DNA repair and reduced recombination during mit
otic growth, with no apparent effect on meiosis, The principal role of RAD5
4 in sister chromatid-based repair may also be shared by mammalian and yeas
t cells.