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Transcription Factor Sp1 Promotes Chromatin Remodeling at DNA Double‐Strand Breaks
Author(s) -
Beishline Kate,
Koduri Sravanthi,
Clifford Jane
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.969.7
Subject(s) - genome instability , dna damage , chromatin remodeling , chromatin , dna repair , histone , biology , microbiology and biotechnology , nucleosome , transcription factor , dna , genetics , gene
DNA damage is intimately associated with cancer and aging. The DNA damage response (DDR) is complex, with pathways that sense lesions, signal cell‐cycle arrest, and repair damaged DNA to prevent mutations. Transcription factor Specificity Protein 1 (Sp1) is phosphorylated in response to DNA damage and recruited to sites of Double Strand Breaks (DSBs). We have determined Sp1 is required for DSB repair. The N‐terminal 182 amino acids of Sp1 are sufficient for localization to DSBs and while it retains no transcriptional activity, this domain is sufficient to rescue the repair defect in Sp1‐depleted cells, suggesting a direct role in repair. We have shown a unique interaction between Sp1 and the MRN complex member, Nbs1, which likely promotes its recruitment. Sp1 mediates chromatin remodeling at promoters and our data suggest that Sp1 plays a similar role at DSBs. We have shown that the Sp1 is required for recruitment of the acetyl‐transferase p300 to break sites, which acetylates histone H3 on Lysine 18. This modification, and others promote nucleosome displacement at break sites to allow for repair factor recruitment. Sp1 expression is modulated in multiple cancers and investigating the role of Sp1 in DNA repair is essential for a mechanistic understanding of damage signaling. This study will provide insights into genomic instability, as well as novel therapeutic targets.