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Molecular and Cellular Biology, August 2001, p. 5156-5168, Vol. 21, No. 15
Wellcome Trust Centre for Cell Biology,
Institute of Cell and Molecular Biology, University of Edinburgh,
Edinburgh EH9 3JR, United Kingdom,1 and
Chiron Corporation, Emeryville, California
94608-29162
Received 10 November 2000/Returned for modification 7 December
2000/Accepted 26 April 2001
Two alleles of the Drosophila melanogaster Rfc4
(DmRfc4) gene, which encodes subunit 4 of the
replication factor C (RFC) complex, cause striking defects in mitotic
chromosome cohesion and condensation. These mutations produce larval
phenotypes consistent with a role in DNA replication but also result in
mitotic chromosomal defects appearing either as premature chromosome
condensation-like or precocious sister chromatid separation figures.
Though the DmRFC4 protein localizes to all replicating nuclei, it is
dispersed from chromatin in mitosis. Thus the mitotic defects appear
not to be the result of a direct role for RFC4 in chromosome structure. We also show that the mitotic defects in these two
DmRfc4 alleles are the result of aberrant checkpoint
control in response to DNA replication inhibition or damage to
chromosomes. Not all surveillance function is compromised in these
mutants, as the kinetochore attachment checkpoint is operative.
Intriguingly, metaphase delay is frequently observed with the more
severe of the two alleles, indicating that subsequent chromosome
segregation may be inhibited. This is the first demonstration that
subunit 4 of RFC functions in checkpoint control in any organism, and
our findings additionally emphasize the conserved nature of RFC's
involvement in checkpoint control in multicellular eukaryotes.
0270-7306/01/$04.00+0 DOI: 10.1128/MCB.21.15.5156-5168.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.
Loss of Cell Cycle Checkpoint Control in Drosophila
Rfc4 Mutants


*
Corresponding author. Mailing address: University of
Edinburgh, Institute of Cell and Molecular Biology, Wellcome Trust
Centre for Cell Biology, Michael Swann Building, King's Buildings,
Mayfield Rd., Edinburgh EH9 3JR, United Kingdom. Phone: 44 (0) 131 650 7114. Fax: 44 (0) 131 650 7778. E-mail:
margarete.heck{at}ed.ac.uk.
Present address: University of Glasgow, Institute of Biological
and Life Sciences, Division of Molecular Genetics, Glasgow G11 6NU,
United Kingdom.
Present address: Zentrum fur Molekulare Biologie, Universitat
Heidelberg, Heidelberg 69120, Germany.
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