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Journal article
Sp1 Facilitates DNA Double-Strand Break Repair through a Nontranscriptional Mechanism
Molecular and cellular biology, v 32(18), pp 3790-3799
01 Sep 2012
PMID: 22826432
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Sp1 is a ubiquitously expressed transcription factor that is phosphorylated by ataxia telangiectasia mutated kinase (ATM) in response to ionizing radiation and H2O2. Here, we show by indirect immunofluorescence that Sp1 phosphorylated on serine 101 (pSp1) localizes to ionizing radiation-induced foci with phosphorylated histone variant gamma H2Ax and members of the MRN (Mre11, Rad50, and Nbs1) complex. More precise analysis of occupancy of DNA double-strand breaks (DSBs) by chromatin immunoprecipitation (ChIP) shows that Sp1, like Nbs1, resides within 200 bp of DSBs. Using laser microirradiation of cells, we demonstrate that pSp1 is present at DNA DSBs by 7.5 min after induction of damage and remains at the break site for at least 8 h. Depletion of Sp1 inhibits repair of site-specific DNA breaks, and the N-terminal 182-amino-acid peptide, which contains targets of ATM kinase but lacks the zinc finger DNA binding domain, is phosphorylated, localizes to DSBs, and rescues the repair defect resulting from Sp1 depletion. Together, these data demonstrate that Sp1 is rapidly recruited to the region immediately adjacent to sites of DNA DSBs and is required for DSB repair, through a mechanism independent of its sequence-directed transcriptional effects.
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Details
- Title
- Sp1 Facilitates DNA Double-Strand Break Repair through a Nontranscriptional Mechanism
- Creators
- Kate Beishline - Drexel UniversityCrystal M. Kelly - Drexel UniversityBeatrix A. Olofsson - Drexel UniversitySravanthi Koduri - Drexel UniversityJacqueline Emrich - Drexel UniversityRoger A. Greenberg - cDepartment of Cancer Biology, Abramson Family Cancer Research Institute, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania, USAJane Azizkhan-Clifford - Drexel University
- Publication Details
- Molecular and cellular biology, v 32(18), pp 3790-3799
- Publisher
- Amer Soc Microbiology
- Number of pages
- 10
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology; [Retired Faculty]
- Web of Science ID
- WOS:000308416600015
- Scopus ID
- 2-s2.0-84866396842
- Other Identifier
- 991019168887804721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology