Submitted to: European Molecular Biology
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 4/30/1996
Publication Date: N/A
Citation: Interpretive Summary: For normal cell division to occur, DNA replication must be completed prior to segregation of the DNA-containing chromosomes. In this study, molecular genetic and biochemical techniques were used to investigate the DNA replication phase of the cell division cycle in the filamentous fungus Aspergillus nidulans, a model system microorganism. Specifically, we investigated the relationships between three genetic elements (p34**cdc2, NIMA, and BIME) in cell division cycle regulation together with their roles in the DNA synthesis phase checkpoint controls linking initiation of cell division to completion of DNA replication. This study uncovered the existence of two DNA synthesis phase checkpoint regulatory systems that control initiation of cell division in A. nidulans. A model is provided describing how these essential genes and their gene products function during cell division
Technical Abstract: There are two S-phase checkpoints controlling mitosis in Aspergillus. The first monitors the rate of DNA replication and inhibits mitosis via Tyr15 phosphorylation of p34**cdc2. Cells unable to phosphorylate p34**cdc2 at Tyrl15 therefore enter mitosis prematurely, in a NIMA dependent manner, when S-phase is slowed. Non-Tyrl15 phosphorylated p34**cdc2 does not, however, promote mitosis if DNA replication is arrested demonstrating the presence of a second checkpoint, which involves BIME. Lack of BIME does not further deregulate the activity of non-Tyr15 phosphorylated p34**cdc2 but lack of BIME and non-Tyr15 phosphorylated p34**cdc2 together cause precocious activation of NIMA during S-phase arrest and promote lethal premature mitosis.