Retinoblastoma protein enhances the fidelity of chromosome segregation mediated by hsHec1p

Retinoblastoma protein (Rb) plays important roles in cell cycle progression and cellular differentiation. It may also participate in hi phase events, although heretofore only circumstantial evidence has suggested such involve ment. Here we show that Rb interacts, through an IxCxE motif and specifical ly during G(2)/M phase, with hsHec1p, a protein essential for proper chromo some segregation. The interaction between Rb and hsHec1p was reconstituted in a yeast strain in which human hsHEC1 rescues the null mutation of scHEC1 . Expression of Rb reduced chromosome segregation errors fivefold in yeast cells sustained by a temperature-sensitive (ts) hshec1-113 allele and enhan ced the ability of wild-type hsHec1p to suppress lethality caused by a ts s mc1 mutation. The interaction between Hec1p and Smc1p was important for the specific DNA-binding activity of Smc1p. Expression of Rb restored part of the inactivated function of hshec1-113p and thereby increased the DNA-bindi ng activity of Smc1p. Rb thus increased the fidelity of chromosome segregat ion mediated by hsHec1p in a heterologous yeast system.