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PMID:11438670

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Citation

Krause, SA, Loupart, ML, Vass, S, Schoenfelder, S, Harrison, S and Heck, MM (2001) Loss of cell cycle checkpoint control in Drosophila Rfc4 mutants. Mol. Cell. Biol. 21:5156-68

Abstract

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.

Links

PubMed PMC87240 Online version:10.1128/MCB.21.15.5156-5168.2001

Keywords

Alleles; Amino Acid Sequence; Animals; Bromodeoxyuridine/metabolism; Cell Cycle; Cell Nucleus/metabolism; Cells, Cultured; Chromosome Aberrations; Chromosome Disorders; Chromosomes/metabolism; Chromosomes/ultrastructure; Cloning, Molecular; DNA/metabolism; DNA-Binding Proteins/genetics; Drosophila/metabolism; Indoles/metabolism; Larva/metabolism; Microscopy, Fluorescence; Mitosis; Molecular Sequence Data; Mutation; Phylogeny; Polymerase Chain Reaction; Replication Protein C; Salivary Glands/metabolism; Sequence Homology, Amino Acid

Significance

Annotations

Gene product Qualifier GO Term Evidence Code with/from Aspect Extension Notes Status

DROME:RFC2

involved_in

GO:0000077: DNA damage checkpoint signaling

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:RFC2

involved_in

GO:0000076: DNA replication checkpoint signaling

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:RFC2

located_in

GO:0005634: nucleus

ECO:0000314: direct assay evidence used in manual assertion

C

Seeded From UniProt

complete

DROME:RFC2

involved_in

GO:0006260: DNA replication

ECO:0000315: mutant phenotype evidence used in manual assertion

P

Seeded From UniProt

complete

DROME:RFC2

enables

GO:0003677: DNA binding

ECO:0000315: mutant phenotype evidence used in manual assertion

F

Seeded From UniProt

complete


See also

References

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