Journal article
Role of the Exocyst Complex Component Sec6/8 in Genomic Stability
Molecular and cellular biology, Vol.35(21), pp.3633-3645
11/2015
DOI: 10.1128/MCB.00768-15
PMCID: PMC4589602
PMID: 26283729
Abstract
The exocyst is a heterooctomeric complex well appreciated for its role in the dynamic assembly of specialized membrane domains. Accumulating evidence indicates that this macromolecular machine also serves as a physical platform that coordinates regulatory cascades supporting biological systems such as host defense signaling, cell fate, and energy homeostasis. The isolation of multiple components of the DNA damage response (DDR) as exocyst-interacting proteins, together with the identification of Sec8 as a suppressor of the p53 response, suggested functional interactions between the exocyst and the DDR. We found that exocyst perturbation resulted in resistance to ionizing radiation (IR) and accelerated resolution of DNA damage. This occurred at the expense of genomic integrity, as enhanced recombination frequencies correlated with the accumulation of aberrant chromatid exchanges. Sec8 perturbation resulted in the accumulation of ATF2 and RNF20 and the promiscuous accumulation of DDR-associated chromatin marks and Rad51 repairosomes. Thus, the exocyst supports DNA repair fidelity by limiting the formation of repair chromatin in the absence of DNA damage.
Details
- Title: Subtitle
- Role of the Exocyst Complex Component Sec6/8 in Genomic Stability
- Creators
- Michael J Torres - Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas, USARaj K Pandita - Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas, USA The Houston Methodist Research Institute, Houston, Texas, USAOzlem Kulak - Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas, USARakesh Kumar - Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas, USAEtienne Formstecher - Hybrigenics, Inc., Paris, FranceNobuo Horikoshi - The Houston Methodist Research Institute, Houston, Texas, USAKalpana Mujoo - The Houston Methodist Research Institute, Houston, Texas, USAClayton R Hunt - The Houston Methodist Research Institute, Houston, Texas, USAYingming Zhao - Ben May Department for Cancer Research, The University of Chicago, Chicago, Illinois, USALawrence Lum - Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas, USAAubhishek Zaman - Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas, USACharles Yeaman - Department of Anatomy and Cell Biology, University of Iowa, Iowa City, Iowa, USAMichael A White - Department of Cell Biology, University of Texas Southwestern Medical Center, Dallas, Texas, USA Michael.White@UTSouthwestern.edu tpandita@houstonmethodist.orgTej K Pandita - Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas, USA The Houston Methodist Research Institute, Houston, Texas, USA Michael.White@UTSouthwestern.edu tpandita@houstonmethodist.org
- Resource Type
- Journal article
- Publication Details
- Molecular and cellular biology, Vol.35(21), pp.3633-3645
- DOI
- 10.1128/MCB.00768-15
- PMID
- 26283729
- PMCID
- PMC4589602
- NLM abbreviation
- Mol Cell Biol
- ISSN
- 0270-7306
- eISSN
- 1098-5549
- Publisher
- United States
- Grant note
- R01 CA154320 / NCI NIH HHS P30 CA142543 / NCI NIH HHS R01 CA129451 / NCI NIH HHS R01 GM109768 / NIGMS NIH HHS CA129537 / NCI NIH HHS R35 CA197717 / NCI NIH HHS GM109768 / NIGMS NIH HHS CA71443 / NCI NIH HHS R01 CA129537 / NCI NIH HHS R01 CA071443 / NCI NIH HHS CA129451 / NCI NIH HHS CA154320 / NCI NIH HHS
- Language
- English
- Date published
- 11/2015
- Academic Unit
- Anatomy and Cell Biology; Internal Medicine
- Record Identifier
- 9984025305802771
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