We
have previously shown that TRF4 (Topoisomerase Related Function) is
involved in mitotic chromosome condensation and that the protein
physically associates with SMC proteins, which are known to be required
for several aspects of higher order chromosome structure including
condensation and sister chromatid cohesion. The TRF4 gene was identified
in a screen for gene products with functional redundancy with DNA
topoisomerase I (TOP1) and shares limited homology with TOP1. Recent
findings indicate that TRF4 is also required for proper sister chromatid
cohesion as determined by both fluorescence in situ hybridization and
GFP chromosome assays. In addition, genetic interactions were observed
between trf4 mutations and mutant alleles of two other genes required
for cohesion, SCC1/MCD1 and SMC1. Since we have previously demonstrated
a physical association between Trf4p and Smc1p, the Trf4p is likely to
function in cohesion as part of, or in association with, the SMC1
protein complex. We have found that TRF4 is also required for
recombinational repair of double strand breaks, but not repair of UV-induced damage, suggesting that some of the proteins required for sister
chromatid cohesion also participate in recombinational DNA repair. TRF4
is highly conserved evolutionarily suggesting that it functions
similarly in larger eukaryotes.
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