We isolated mutants of Saccharomyces cerevisiae that lose a 100 kb linear yeast 
artificial chromosome (YAC) at elevated rates. Mutations in two of these LCS 
(linear chromosome stability) genes had little or no effect on the loss rate of 
a circular YAC that had the same centromere and origin of replication as present 
on the linear YAC. Moreover, mutations in these LCS genes also increased the 
loss rate of an authentic linear yeast chromosome, chromosome III, but had only 
small effects on the loss rate of a circular derivative of chromosome III. As 
these mutants preferentially destabilize linear chromosomes, they may affect 
chromosome stability through interactions at telomeres. Telomeres are thought to 
be essential for the protection and complete replication of chromosome ends. The 
cytological properties of telomeres suggest that these structures may play 
additional roles in chromosome function. The lengths of the terminal C1-3A 
repeats at the ends of yeast chromosomes were unaltered in the linear 
preferential lcs mutants, suggesting that these mutants do not affect the 
replication or protection of telomeric DNA. Thus, the linear-preferential lcs 
mutants may identify a role for telomeres in chromosome stability that is 
distinct from their function in the replication and protection of chromosomal 
termini.