Drosophila Ctf4 is essential for genome stability and normal cell cycle progression

Abstract

Proper DNA replication and well-timed cell cycle progression are vital to the normal functioning of a cell. Precise coordination between these mechanisms' constituent proteins ensures their processivity while safeguarding against DNA damage. The Ctf4 protein is a central member of the replication fork and links the replicative MCM helicase and polymerase [alpha]-primase. In addition, it has been implicated as a member of a complex that promotes replication fork stability, the Fork Protection Complex (FPC). This investigation represents the first phenotypic analysis of the function of the Ctf4 protein within a multicellular organism model. We show that Ctf4 interacts with Polymerase [alpha], MCM2, Psf1, and Psf2. We also demonstrate that knockdown of this central replication fork component via a GAL4-UAS RNAi system results in a lower frequency of mitosis due to an S-phase delay, endoreplication defects, as well as mitotic bridging in early embryonic development.