YEAST PRE-MEIOTIC DNA-REPLICATION UTILIZES MITOTIC ORIGIN ARS1 INDEPENDENTLY OF CDC7 FUNCTION

In budding yeast, mitotic DNA replication initiates at sequence-specif ic replication origins, the prototype for which is ARS1. Initiation se rves as the primary control point for mitotic DNA replication, and is catalyzed by the Cdc7 protein kinase. In contrast, premeiotic DNA repl ication apparently docs not require Cdc7, and the existence and nature of specific replication origins in the meiotic division cycle have no t been previously reported. We have begun to investigate the mechanism of premeiotic DNA synthesis by determining whether or not ARS1 functi ons as a DNA replication origin in meiosis. We have taken advantage of the fact that transcription through ARS1 disrupts its ability to func tion as an origin to show that ARS1 is required for premeiotic DNA rep lication of a plasmid bearing this element. Further, premeiotic replic ation from ARS1 still occurs in a cdc7 mutant strain held at condition s non-permissive for Cdc7 protein kinase activity. These findings reve al that premeiotic DNA replication can initiate from origins also used in mitosis, and is not regulated by Cdc7. Taken together with previou s findings implicating Cdc7 in meiotic DNA recombination and induced m utagenesis, these findings prompt us to postulate that the Cdc7 protei n kinase regulates some step common to several DNA metabolic processes such as local disassembly of chromatin or activation of a key compone nt of the DNA metabolic machinery.