Genetics, Vol. 149, 1221-1233, July 1998, Copyright © 1998

Fission Yeast cdc24+ Encodes a Novel Replication Factor Required for Chromosome Integrity

Kathleen L. Goulda, C. Geoffrey Burnsa, Anna Feoktistovaa, Ching-Pei Hua, Sally G. Pasionb, and Susan L. Forsburgb
a Howard Hughes Medical Institute and Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, Tennessee 38232
b Molecular Biology and Virology Laboratory, The Salk Institute, La Jolla, California 92037

Corresponding author: Kathleen L. Gould, B2309 MCN, 1161 21st Ave. S., Nashville, TN 37232, kathy.gould{at}mcmail.vanderbilt.edu (E-mail).

Communicating editor: P. G. YOUNG

A mutation within the Schizosaccharomyces pombe cdc24+ gene was identified previously in a screen for cell division cycle mutants and the cdc24+ gene was determined to be essential for S phase in this yeast. We have isolated the cdc24+ gene by complementation of a new temperature-sensitive allele of the gene, cdc24-G1. The DNA sequence predicts the presence of an open reading frame punctuated by six introns which encodes a pioneer protein of 58 kD. A cdc24 null mutant was generated by homologous recombination. Haploid cells lacking cdc24+ are inviable, indicating that cdc24+ is an essential gene. The transcript of cdc24+ is present at constant levels throughout the cell cycle. Cells lacking cdc24+ function show a checkpoint-dependent arrest with a 2N DNA content, indicating a block late in S phase. Arrest is accompanied by a rapid loss of viability and chromosome breakage. An S. pombe homolog of the replicative DNA helicase DNA2 of S. cerevisiae suppresses cdc24. These results suggest that Cdc24p plays a role in the progression of normal DNA replication and is required to maintain genomic integrity.




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