Effects of Extracellular Matix on DNA Repair in Vivo
Abstract
DNA damage in the form of double-strand breaks is caused by exposure to endogenous factors as well as in response to radiation therapy in breast cancer patients. Double-strand breaks can be repaired by homologous recombination or nonhomologous end joining pathways, both of which can lead to error-prone repair. Errors in repair lead to accumulation of mutations that may accelerate the process of tumorigenesis and malignant transformation. Apart from cell cycle effects, little is known about which factors contribute to the determination of double-strand break efficiency or pathway choices in mammalian cells. We previously showed that extracellular matrix signaling can regulate double-strand break repair pathway choice in a human breast epithelial cell line. Furthermore, we find that the kinetics of foci formation by a DNA damage signaling protein after ionizing radiation is altered by extracellular matrix signaling. Here we found that in primary mouse mammary epithelial cells extracellular matrix signaling regulates double-strand repair, as well as the kinetics of damage signaling after ionizing radiation. Having shown that the effects of ECM on DNA damage signaling and repair are generalizable, we will use mouse models with altered extracellular matrix signaling or DNA repair components to genetically dissect this pathway in vivo.
Document Details
- Document Type
- Technical Report
- Publication Date
- Sep 01, 2006
- Accession Number
- ADA468527
Entities
People
- Aylin Rizki
Organizations
- University of California, Berkeley