DNA43, also known as MCM10, is an essential gene that was independently identified in a screen for temperature sensitive mutants (5) and in a screen for mutations that cause defects in the stability of centromeric plasmids (minichromosome maintenance defects, Mcm^-) (3, 6). The phenotypes of dna43 mutants strongly suggest that Dna43p plays a role in the initiation of DNA replication. The temperature sensitive dna43-1 allele causes cells to arrest with large buds and unreplicated DNA at the restrictive temperature (5). In addition to its Mcm^- defect, the mcm10-1 allele also reduces the frequency of DNA replication initiation at chromosomal origins, and causes DNA replication forks to pause during elongation at origins that have not initiated (3). The pausing depends on the integrity of sequences essential for origin function that are occupied by the pre-replicative complex (pre-RC) prior to initiation (2, 6). The pre-RC is an assembly of proteins that forms at origins of DNA replication between late M phase and the G1/S transition, and includes proteins believed to act in DNA replication initiation (7, 8, 9, 10, 11). Dna43p interacts physically and genetically with members of the Mcm2-7 family, which are pre-RC components required for the initiation of DNA replication (3, 2, 6). Dna43p is associated with chromatin throughout the cell cycle, and its presence is required for Mcm2p, but not the origin recognition complex subunit Orc3p, to bind chromatin in G1 (2). The S. pombe Cdc23 protein is 22% identical to Dna43p and can complement the dna43-1 mutation (12).

Last updated: 2000-05-10