Rif1, originally recognized for its role at telomeres in budding yeast, has been 
implicated in a wide variety of cellular processes in mammals, including 
pluripotency of stem cells, response to double-strand breaks, and breast cancer 
development. As the molecular function of Rif1 is not known, we examined the 
consequences of Rif1 deficiency in mouse cells. Rif1 deficiency leads to failure 
in embryonic development, and conditional deletion of Rif1 from mouse embryo 
fibroblasts affects S-phase progression, rendering cells hypersensitive to 
replication poisons. Rif1 deficiency does not alter the activation of the DNA 
replication checkpoint but rather affects the execution of repair. RNA 
interference to human Rif1 decreases the efficiency of homology-directed repair 
(HDR), and Rif1 deficiency results in aberrant aggregates of the HDR factor 
Rad51. Consistent with a role in S-phase progression, Rif1 accumulates at 
stalled replication forks, preferentially around pericentromeric 
heterochromatin. Collectively, these findings reveal a function for Rif1 in the 
repair of stalled forks by facilitating HDR.