Large-scale synthetic genetic array analysis links various aspects of
chromosome dynamics.
Hong Xu (1), Michael Chang (2), Marie Evangelista (1), Ainslie
Parsons (1), Bernhard Suter (3), Jasper Rine (3), Grant Brown (2),
Charlie Boone (1)
(1) Banting and Best Department , University of Toronto, 112 College,
Toronto, ON M5G 1L6, Canada;
(2) Room 5326, The Department of Biochemistry, University of Toronto,
ON, M5S 1A8, Canada;
(3) University of California, Berkeley, Department of Molecular & Cell
Biology,401 Barker Hall #3202, Berkeley, CA 94720-3202
The accurate duplication and segregation of the genome involves a
complex network of interacting pathways. A large-scale synthetic genetic
array (SGA) analysis was applied in order to understand the
relationships among these different pathways. We have conducted SGA
screens in Saccharomyces cerevisiae with over 20 genes involved
in the replication, repair, and segregation of DNA. Many genes
traditionally thought to function in only one of these paths appear to
have multiple roles, suggesting that seemingly unrelated pathways
involved in different aspects of chromosome dynamics are actually
intimately linked. For example, CDC7 is an essential gene that is
required for the initiation of DNA replication. 47 deletion mutants
interacted genetically with the cdc7-1 allele, and many of these have
roles in DNA damage repair, checkpoint activation, and sister chromatid
cohesion. SGA analysis also shows remarkable value in discovering novel
genes involved in one or more of these processes. Several
uncharacterized ORFs were synthetically lethal with multiple DNA damage
components and are predicted to be potential members of DNA damage
response pathways. With the continuous accumulation of SGA data and the
use of data mining techniques, a comprehensive interaction map of
synthetic genetic interactions will be generated, giving us a better
understanding of how different pathways work together to ensure the
accurate duplication and segregation of the genome.
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