DOI: 10.1242/dev.128.9.1697. <i>Orc</i> mutants arrest in metaphase with abnormally condensed chromosomes

Orc mutants arrest in metaphase with abnormally condensed chromosomes

10.1242/dev.128.9.1697

Crossref journal-article

The Company of Biologists

Development (237)

Abstract

ABSTRACT The origin recognition complex (ORC) is a six subunit complex required for eukaryotic DNA replication initiation and for silencing of the heterochromatic mating type loci in Saccharomyces cerevisiae. Our discovery of the Drosophila ORC complex concentrated in the centric heterochromatin of mitotic cells in the early embryo and its interactions with heterochromatin protein 1 (HP-1) lead us to speculate that ORC may play some general role in chromosomal folding. To explore the role of ORC in chromosomal condensation, we have identified a mutant of subunit 5 of the Drosophila melanogaster origin recognition complex (Orc5) and have characterized the phenotypes of both the Orc5 and the previously identified Orc2 mutant, k43. Both Orc mutants died at late larval stages and surprisingly, despite a reduced number of S-phase cells, an increased fraction of cells were also detected in mitosis. For this latter population of cells, Orc mutants arrest in a defective metaphase with shorter and thicker chromosomes that fail to align at the metaphase plate within a poorly assembled mitotic spindle. In addition, sister chromatid cohesion was frequently lost. PCNA and MCM4 mutants had similar phenotypes to Orc mutants. We propose that DNA replication defects trigger the mitotic arrest, due to the fact that frequent fragmentation was observed. Thus, cells have a mitotic checkpoint that senses chromosome integrity. These studies also suggest that the density of functional replication origins and completion of S phase are requirements for proper chromosomal condensation.

Bibliography

Pflumm, M. F., & Botchan, M. R. (2001). Orc mutants arrest in metaphase with abnormally condensed chromosomes. Development, 128(9), 1697â1707.

Authors 2

Michelle F. Pflumm (first)
Michael R. Botchan (additional)

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Dates

Type	When
Created	4 years, 4 months ago (April 26, 2021, 12:50 a.m.)
Deposited	2 years, 6 months ago (Feb. 27, 2023, 6:07 p.m.)
Indexed	1 month, 2 weeks ago (July 14, 2025, 11:16 p.m.)
Issued	24 years, 3 months ago (May 1, 2001)
Published	24 years, 3 months ago (May 1, 2001)
Published Online	24 years, 3 months ago (May 1, 2001)
Published Print	24 years, 3 months ago (May 1, 2001)

Funders 0

None

BibTeX

@article{Pflumm_2001, title={Orc mutants arrest in metaphase with abnormally condensed chromosomes}, volume={128}, ISSN={1477-9129}, url={http://dx.doi.org/10.1242/dev.128.9.1697}, DOI={10.1242/dev.128.9.1697}, number={9}, journal={Development}, publisher={The Company of Biologists}, author={Pflumm, Michelle F. and Botchan, Michael R.}, year={2001}, month=may, pages={1697–1707} }

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