Display Settings:


Send to:

Choose Destination
See comment in PubMed Commons below
Neoplasia. 2005 Nov;7(11):1011-9.

The Polycomb group protein EZH2 impairs DNA repair in breast epithelial cells.

Author information

  • 1Department of Pathology, University of Michigan, Arbor, MI, USA.


The Polycomb group protein EZH2 is a transcriptional repressor involved in controlling cellular memory and has been linked to aggressive and metastatic breast cancer. Here we report that EZH2 decreased the expression of five RAD51 paralog proteins involved in homologous recombination (HR) repair of DNA double-strand breaks (RAD51B/RAD51L1, RAD51C/RAD51L2, RAD51D/RAD51L3, XRCC2, and XRCC3), but did not affect the levels of DMC1, a gene that only functions in meiosis. EZH2 overexpression impaired the formation of RAD51 repair foci at sites of DNA breaks. Overexpression of EZH2 resulted in decreased cell survival and clonogenic capacity following DNA damage induced independently by etoposide and ionizing radiation. We suggest that EZH2 may contribute to breast tumorigenesis by specific downregulation of RAD51-like proteins and by impairment of HR repair. We provide mechanistic insights into the function of EZH2 in mammalian cells and uncover a link between EZH2, a regulator of homeotic gene expression, and HR DNA repair. Our study paves the way for exploring the blockade of EZH2 overexpression as a novel approach for the prevention and treatment of breast cancer.

[PubMed - indexed for MEDLINE]
Free PMC Article

Images from this publication.See all images (3)Free text

Figure 1
Figure 2
Figure 3
PubMed Commons home

PubMed Commons

How to join PubMed Commons

    Supplemental Content

    Icon for PubMed Central
    Loading ...
    Write to the Help Desk