Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress 2023 EHA Congress 2023 ASCO Annual Meeting
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Breast Cancer Research
Published in: Breast Cancer Research 3/2011

01-06-2011 | Editorial

Spotlight on Geminin

Author: Melvin L DePamphilis

Published in: Breast Cancer Research | Issue 3/2011

Login to get access

Abstract

In the previous issue of Breast Cancer Research, Gardner and co-workers describe a novel interaction between Geminin, a protein that prevents reinitiation of DNA replication, and Topoisomerase IIα (TopoIIα), an enzyme essential for removing catenated intertwines between sister chromatids. Geminin facilitates the action of TopoIIα, thereby promoting termination of DNA replication at the same time it inhibits initiation. In this manner, Geminin ensures that cells duplicate their genome once, but only once, each time they divide. Remarkably, either depletion of Geminin or over-expression of Geminin inhibits the action of TopoIIα, thereby making Geminin an excellent target for cancer chemotherapy.
Literature
1.
Gardner L, Malik R, Shimizu Y, Mullins N, ElShamy WM: Geminin overexpression prevents the completion of topoisomerase IIα chromosome decatenation leading to aneuploidy in human mammary epithelial cells. Breast Cancer Res. 2011, 13: R53-10.1186/bcr2884.CrossRefPubMedPubMedCentral
2.
DePamphilis ML: DNA Replication and Human Disease. 2006, Cold Spring Harbor, NY: Cold Spring Harbor Laboratory Press
3.
Lim JW, Hummert P, Mills JC, Kroll KL: Geminin cooperates with Polycomb to restrain multi-lineage commitment in the early embryo. Development. 2011, 138: 33-44. 10.1242/dev.059824.CrossRefPubMedPubMedCentral
4.
Yellajoshyula D, Patterson ES, Elitt MS, Kroll KL: Geminin promotes neural fate acquisition of embryonic stem cells by maintaining chromatin in an accessible and hyperacetylated state. Proc Natl Acad Sci USA. 2011, 108: 3294-3299. 10.1073/pnas.1012053108.CrossRefPubMedPubMedCentral
5.
Miotto B, Struhl K: HBO1 histone acetylase activity is essential for DNA replication licensing and inhibited by Geminin. Mol Cell. 2010, 37: 57-66. 10.1016/j.molcel.2009.12.012.CrossRefPubMedPubMedCentral
6.
Falaschi A, Abdurashidova G, Biamonti G: DNA replication, development and cancer: a homeotic connection?. Crit Rev Biochem Mol Biol. 2010, 45: 14-22. 10.3109/10409230903365608.CrossRefPubMed
7.
Lutzmann M, Mechali M: MCM9 binds Cdt1 and is required for the assembly of prereplication complexes. Mol Cell. 2008, 31: 190-200. 10.1016/j.molcel.2008.07.001.CrossRefPubMed
8.
Haruki T, Shomori K, Hamamoto Y, Taniguchi Y, Nakamura H, Ito H: Geminin expression in small lung adenocarcinomas: implication of prognostic significance. Lung Cancer. 2011, 71: 356-362. 10.1016/j.lungcan.2010.06.013.CrossRefPubMed
9.
Zhu W, Depamphilis ML: Selective killing of cancer cells by suppression of geminin activity. Cancer Res. 2009, 69: 4870-4877. 10.1158/0008-5472.CAN-08-4559.CrossRefPubMedPubMedCentral
10.
Lee J, Kim JA, Margolis RL, Fotedar R: Substrate degradation by the anaphase promoting complex occurs during mitotic slippage. Cell Cycle. 2010, 9: 1792-1801. 10.4161/cc.9.9.11519.CrossRefPubMedPubMedCentral
11.
Nakuci E, Xu M, Pujana MA, Valls J, Elshamy WM: Geminin is bound to chromatin in G2/M phase to promote proper cytokinesis. Int J Biochem Cell Biol. 2006, 38: 1207-1220. 10.1016/j.biocel.2005.12.017.CrossRefPubMed
12.
Schultz KM, Banisadr G, Lastra RO, McGuire T, Kessler JA, Miller RJ, McGarry TJ: Geminin-deficient neural stem cells exhibit normal cell division and normal neurogenesis. PLoS One. 2011, 6: e17736-10.1371/journal.pone.0017736.CrossRefPubMedPubMedCentral
13.
Shinnick KM, Eklund EA, McGarry TJ: Geminin deletion from hematopoietic cells causes anemia and thrombocytosis in mice. J Clin Invest. 2010, 120: 4303-4315. 10.1172/JCI43556.CrossRefPubMedPubMedCentral
14.
Shreeram S, Sparks A, Lane DP, Blow JJ: Cell type-specific responses of human cells to inhibition of replication licensing. Oncogene. 2002, 21: 6624-6632. 10.1038/sj.onc.1205910.CrossRefPubMedPubMedCentral
15.
16.
Nevis KR, Cordeiro-Stone M, Cook JG: Origin licensing and p53 status regulate Cdk2 activity during G(1). Cell Cycle. 2009, 8: 1952-1963. 10.4161/cc.8.12.8811.CrossRefPubMedPubMedCentral
Metadata
Title
Spotlight on Geminin
Author
Melvin L DePamphilis
Publication date
01-06-2011
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 3/2011
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr2881

Other articles of this Issue 3/2011

Breast Cancer Research 3/2011 Go to the issue

Research article

Elevated pre-treatment levels of plasma C-reactive protein are associated with poor prognosis after breast cancer: a cohort study

Research article

Elevated insulin-like growth factor 1 receptor signaling induces antiestrogen resistance through the MAPK/ERK and PI3K/Akt signaling routes

Review

Microarrays in the 2010s: the contribution of microarray-based gene expression profiling to breast cancer classification, prognostication and prediction

Editorial

miR-200c at the nexus of epithelial-mesenchymal transition, resistance to apoptosis, and the breast cancer stem cell phenotype

Editorial

Jekyll or Hyde: does Matrigel provide a more or less physiological environment in mammary repopulating assays?

Research article

Impact of established prognostic factors and molecular subtype in very young breast cancer patients: pooled analysis of four EORTC randomized controlled trials
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits