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Molecular and Cellular Biology, February 1999, p. 1038-1048, Vol. 19, No. 2
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

Fission Yeast Cdc24 Is a Replication Factor C- and Proliferating Cell Nuclear Antigen-Interacting Factor Essential for S-Phase Completion

Hiroyuki Tanaka,dagger Koichi Tanaka, Hiroshi Murakami,Dagger and Hiroto Okayama*

Department of Biochemistry and Molecular Biology, The University of Tokyo Graduate School of Medicine, Bunkyo-ku, Tokyo 113-0033, Japan

Received 22 September 1998/Returned for modification 16 October 1998/Accepted 2 November 1998

At the nonpermissive temperature the fission yeast cdc24-M38 mutant arrests in the cell cycle with incomplete DNA replication as indicated by pulsed-field gel electrophoresis. The cdc24+ gene encodes a 501-amino-acid protein with no significant homology to any known proteins. The temperature-sensitive cdc24 mutant is effectively rescued by pcn1+, rfc1+ (a fission yeast homologue of RFC1), and hhp1+, which encode the proliferating cell nuclear antigen (PCNA), the large subunit of replication factor C (RFC), and a casein kinase I involved in DNA damage repair, respectively. The Cdc24 protein binds PCNA and RFC1 in vivo, and the domains essential for Cdc24 function and for RFC1 and PCNA binding colocalize in the N-terminal two-thirds of the molecule. In addition, cdc24+ genetically interacts with the gene encoding the catalytic subunit of DNA polymerase varepsilon , which is stimulated by PCNA and RFC, and with those encoding the fission yeast counterparts of Mcm2, Mcm4, and Mcm10. These results indicate that Cdc24 is an RFC- and PCNA-interacting factor required for DNA replication and might serve as a target for regulation.

* Corresponding author. Mailing address: Department of Biochemistry and Molecular Biology, The University of Tokyo Graduate School of Medicine, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033, Japan. Phone: 81-3-5689-0876. Fax: 81-3-3815-1490. E-mail: okayama{at}m.u-tokyo.ac.jp.

dagger Present address: Department of Hygiene and Oncology, The Tokyo Medical and Dental University School of Medicine, Bunkyo-ku, Tokyo 113-8519, Japan.

Dagger Present address: Cell Cycle Laboratory, Imperial Cancer Research Fund, London WC2A 3PX, England.

Molecular and Cellular Biology, February 1999, p. 1038-1048, Vol. 19, No. 2
0270-7306/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


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