title: Drosophila Ctf4 is essential for efficient DNA replication and normal cell cycle progression.
abstract: BACKGROUND
  Proper coordination of the functions at the DNA replication fork is vital to the normal functioning of a cell. Specifically the precise coordination of helicase and polymerase activity is crucial for efficient passage though S phase. The Ctf4 protein has been shown to be a central member of the replication fork and links the replicative MCM helicase and DNA polymerase α primase. In addition, it has been implicated as a member of a complex that promotes replication fork stability, the Fork Protection Complex (FPC), and as being important for sister chromatid cohesion. As such, understanding the role of Ctf4 within the context of a multicellular organism will be integral to our understanding of its potential role in developmental and disease processes.
  
  
  RESULTS
  We find that Drosophila Ctf4 is a conserved protein that interacts with members of the GINS complex, Mcm2, and Polymerase α primase. Using in vivo RNAi knockdown of CTF4 in Drosophila we show that Ctf4 is required for viability, S phase progression, sister chromatid cohesion, endoreplication, and coping with replication stress.
  
  
  CONCLUSIONS
  Ctf4 remains a central player in DNA replication. Our findings are consistent with what has been previously reported for CTF4 function in yeast, Xenopus extracts, and human tissue culture. We show that Ctf4 function is conserved and that Drosophila can be effectively used as a model to further probe the precise function of Ctf4 as a member of the replication fork and possible roles in development.
authors.affiliation: Department of Biology, East Carolina University, Greenville, NC 27858, USA.
authors.forename: Justin A
authors.initials: JA
authors.lastname: Gosnell
authors.forename: Tim W
authors.initials: TW
authors.lastname: Christensen
mesh_terms: D000818:Animals; D018797:Cell Cycle Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism; D004256:DNA Polymerase I / Q000378:metabolism; D004261:DNA Replication; D004330:Drosophila; D029721:Drosophila Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D047108:Embryonic Development; D055785:Gene Knockdown Techniques; D006918:Hydroxyurea / Q000494:pharmacology; D064110:Minichromosome Maintenance Proteins; D034622:RNA Interference; D016196:S Phase
chemical_list: D018797:Cell Cycle Proteins; D002868:Chromosomal Proteins, Non-Histone; C560418:Ctf4 protein, Drosophila; D029721:Drosophila Proteins; D004256:DNA Polymerase I; C555716:MCM2 protein, Drosophila; D064110:Minichromosome Maintenance Proteins; D006918:Hydroxyurea