English
 
Help Privacy Policy Disclaimer
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Cre recombinase induces DNA damage and tetraploidy in the absence of LoxP sites

Janbandhu, V. C., Moik, D., & Fässler, R. (2014). Cre recombinase induces DNA damage and tetraploidy in the absence of LoxP sites. CELL CYCLE, 13(3), 462-470. doi:10.4161/cc.27271.

Item is

Files

show Files

Locators

show

Creators

show
hide
 Creators:
Janbandhu, Vaibhao C1, Author              
Moik, Daniel1, Author              
Fässler, Reinhard1, Author              
Affiliations:
1Fässler, Reinhard / Molecular Medicine, Max Planck Institute of Biochemistry, Max Planck Society, ou_1565147              

Content

show
hide
Free keywords: INTEGRIN-LINKED KINASE; MAMMALIAN-CELLS; TRANSGENIC MICE; CYCLIN B1; MOUSE; GENE; CHROMOSOME; CANCER; BACTERIOPHAGE-P1; ANEUPLOIDYCre recombinase; cytokinesis failure; bypass of mitosis; tetraploidy; aneuploidy; cancer; DNA damage; transgenic mice; homologous recombination; apoptosis;
 Abstract: The spatiotemporal manipulations of gene expression by the Cre recombinase (Cre) of bacteriophage P1 has become an essential asset to understanding mammalian genetics. Accumulating evidence suggests that Cre activity can, in addition to excising targeted loxP sites, induce cytotoxic effects, including abnormal cell cycle progression, genomic instability, and apoptosis, which can accelerate cancer progression. It is speculated that these defects are caused by Cre-induced DNA damage at off-target sites. Here we report the formation of tetraploid keratinocytes in the epidermis of keratin 5 and/or keratin 14 promoter-driven Cre (KRT5- and KRT14-Cre) expressing mouse skin. Biochemical analyses and flow cytometry demonstrated that Cre expression also induces DNA damage, genomic instability, and tetraploidy in HCT116 cells, and live-cell imaging revealed an extension of the G(2) cell cycle phase followed by defective or skipping of mitosis as cause for the tetraploidy. Since tetraploidy eventually leads to aneuploidy, a hallmark of cancer, our findings highlight the importance of distinguishing non-specific cytopathic effects from specific Cre/loxP-driven genetic manipulations when using Cre-mediated gene deletions.

Details

show
hide
Language(s): eng - English
 Dates: 2014
 Publication Status: Published in print
 Pages: 9
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: ISI: 000332833400022
DOI: 10.4161/cc.27271
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: CELL CYCLE
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA : LANDES BIOSCIENCE
Pages: - Volume / Issue: 13 (3) Sequence Number: - Start / End Page: 462 - 470 Identifier: ISSN: 1538-4101