The Drosophila Geminin Homolog: Roles for Geminin in Limiting DNA Replication, in Anaphase and in Neurogenesis

Overview

Journal Genes Dev

Specialty Molecular Biology

Date 2001 Oct 20

PMID 11641279

Citations 63

Authors

L M Quinn

A Herr

T J McGarry

H Richardson

Affiliations

Soon will be listed here.

Abstract

We have identified a Drosophila homolog of the DNA replication initiation inhibitor Geminin (Dm geminin) and show that it has all of the properties of Xenopus and human Geminin. During Drosophila development, Dm Geminin is present in cycling cells; protein accumulates during S phase and is degraded at the metaphase to anaphase transition. Overexpression of Dm geminin in embryos inhibits DNA replication, but cells enter mitosis arresting in metaphase, as in dup (cdt1) mutants, and undergo apoptosis. Overexpression of Dm Geminin also induces ectopic neural differentiation. Dm geminin mutant embryos exhibit anaphase defects at cycle 16 and increased numbers of S phase cells later in embryogenesis. In a partially female-sterile Dm geminin mutant, excessive DNA amplification in the ovarian follicle cells is observed. Our data suggest roles for Dm Geminin in limiting DNA replication, in anaphase and in neural differentiation.

Citing Articles

The biological principles and advanced applications of DSB repair in CRISPR-mediated yeast genome editing.

Bai W, Huang M, Li C, Li J Synth Syst Biotechnol. 2023; 8(4):584-596.

PMID: 37711546 PMC: 10497738. DOI: 10.1016/j.synbio.2023.08.007.

A repackaged CRISPR platform increases homology-directed repair for yeast engineering.

Ploessl D, Zhao Y, Cao M, Ghosh S, Lopez C, Sayadi M Nat Chem Biol. 2021; 18(1):38-46.

PMID: 34711982 DOI: 10.1038/s41589-021-00893-5.

Replication initiation: Implications in genome integrity.

Lin Y, Prasanth S DNA Repair (Amst). 2021; 103:103131.

PMID: 33992866 PMC: 8296962. DOI: 10.1016/j.dnarep.2021.103131.

Wound-induced polyploidization is driven by Myc and supports tissue repair in the presence of DNA damage.

Grendler J, Lowgren S, Mills M, Losick V Development. 2019; 146(15).

PMID: 31315896 PMC: 6703715. DOI: 10.1242/dev.173005.

interacts with and regulates cell proliferation.

Zhou X, Wei Y, Chen X, Chen P, Tang X, Zhang Q Cell Cycle. 2019; 18(13):1498-1512.

PMID: 31145019 PMC: 6592228. DOI: 10.1080/15384101.2019.1624109.

References

Saka Y, Smith J . Spatial and temporal patterns of cell division during early Xenopus embryogenesis. Dev Biol. 2001; 229(2):307-18. DOI: 10.1006/dbio.2000.0101. View

Biggins S, Murray A . Sister chromatid cohesion in mitosis. Curr Opin Cell Biol. 1999; 10(6):769-75. DOI: 10.1016/s0955-0674(98)80120-8. View

Tada S, Li A, Maiorano D, Mechali M, J Blow J . Repression of origin assembly in metaphase depends on inhibition of RLF-B/Cdt1 by geminin. Nat Cell Biol. 2001; 3(2):107-13. PMC: 3605706. DOI: 10.1038/35055000. View

Lei M, Tye B . Initiating DNA synthesis: from recruiting to activating the MCM complex. J Cell Sci. 2001; 114(Pt 8):1447-54. DOI: 10.1242/jcs.114.8.1447. View

Edgar B . Endoreplication cell cycles: more for less. Cell. 2001; 105(3):297-306. DOI: 10.1016/s0092-8674(01)00334-8. View

J Blow J, Laskey R . A role for the nuclear envelope in controlling DNA replication within the cell cycle. Nature. 1988; 332(6164):546-8. DOI: 10.1038/332546a0. View

Lehner C, Ofarrell P . The roles of Drosophila cyclins A and B in mitotic control. Cell. 1990; 61(3):535-47. PMC: 2753431. DOI: 10.1016/0092-8674(90)90535-m. View

Glotzer M, Murray A, Kirschner M . Cyclin is degraded by the ubiquitin pathway. Nature. 1991; 349(6305):132-8. DOI: 10.1038/349132a0. View

Girdham C, Glover D . Chromosome tangling and breakage at anaphase result from mutations in lodestar, a Drosophila gene encoding a putative nucleoside triphosphate-binding protein. Genes Dev. 1991; 5(10):1786-99. DOI: 10.1101/gad.5.10.1786. View

10.

Wolff T, Ready D . The beginning of pattern formation in the Drosophila compound eye: the morphogenetic furrow and the second mitotic wave. Development. 1991; 113(3):841-50. DOI: 10.1242/dev.113.3.841. View

11.

Richardson H, OKeefe L, Marty T, Saint R . Ectopic cyclin E expression induces premature entry into S phase and disrupts pattern formation in the Drosophila eye imaginal disc. Development. 1995; 121(10):3371-9. DOI: 10.1242/dev.121.10.3371. View

12.

de Nooij J, Hariharan I . Uncoupling cell fate determination from patterned cell division in the Drosophila eye. Science. 1995; 270(5238):983-5. DOI: 10.1126/science.270.5238.983. View

13.

Edgar B, Lehner C . Developmental control of cell cycle regulators: a fly's perspective. Science. 1996; 274(5293):1646-52. DOI: 10.1126/science.274.5293.1646. View

14.

King R, Deshaies R, Peters J, Kirschner M . How proteolysis drives the cell cycle. Science. 1996; 274(5293):1652-9. DOI: 10.1126/science.274.5293.1652. View

15.

Bhat M, Philp A, Glover D, Bellen H . Chromatid segregation at anaphase requires the barren product, a novel chromosome-associated protein that interacts with Topoisomerase II. Cell. 1996; 87(6):1103-14. DOI: 10.1016/s0092-8674(00)81804-8. View

16.

Mahbubani H, Chong J, Chevalier S, Thommes P, J Blow J . Cell cycle regulation of the replication licensing system: involvement of a Cdk-dependent inhibitor. J Cell Biol. 1997; 136(1):125-35. PMC: 2132454. DOI: 10.1083/jcb.136.1.125. View

17.

Thommes P, Kubota Y, Takisawa H, J Blow J . The RLF-M component of the replication licensing system forms complexes containing all six MCM/P1 polypeptides. EMBO J. 1997; 16(11):3312-9. PMC: 1169947. DOI: 10.1093/emboj/16.11.3312. View

18.

Roch F, Serras F, Cifuentes F, Corominas M, Alsina B, Amoros M . Screening of larval/pupal P-element induced lethals on the second chromosome in Drosophila melanogaster: clonal analysis and morphology of imaginal discs. Mol Gen Genet. 1998; 257(2):103-12. DOI: 10.1007/pl00008620. View

19.

Calvi B, Lilly M, Spradling A . Cell cycle control of chorion gene amplification. Genes Dev. 1998; 12(5):734-44. PMC: 316579. DOI: 10.1101/gad.12.5.734. View

20.

Ohnuma S, Philpott A, Wang K, Holt C, Harris W . p27Xic1, a Cdk inhibitor, promotes the determination of glial cells in Xenopus retina. Cell. 1999; 99(5):499-510. DOI: 10.1016/s0092-8674(00)81538-x. View