Phosphorylation of HIC1 (Hypermethylated in Cancer 1) Ser694 by ATM is essential for DNA repair
| العنوان: | Phosphorylation of HIC1 (Hypermethylated in Cancer 1) Ser694 by ATM is essential for DNA repair |
|---|---|
| المؤلفون: | Marion Dubuissez, Vanessa Dehennaut, Sonia Paget, Nathalie Spruyt, Ingrid Loison, Adeline Page, Dominique Leprince |
| المصدر: | Biochemical and biophysical research communications. 553 |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, DNA Repair, DNA repair, Biophysics, SUMO protein, Kruppel-Like Transcription Factors, Ataxia Telangiectasia Mutated Proteins, Biochemistry, Cell Line, Serine, 03 medical and health sciences, chemistry.chemical_compound, Phosphoserine, 0302 clinical medicine, Animals, Humans, Phosphorylation, Molecular Biology, Conserved Sequence, Zinc finger, Chemistry, Kinase, Cell Biology, Cell biology, 030104 developmental biology, Acetylation, 030220 oncology & carcinogenesis, Comet Assay, DNA, DNA Damage |
| الوصف: | The tumor suppressor gene HIC1 (Hypermethylated in Cancer 1) encodes a transcriptional repressor involved in the DNA-damage response. A SUMOylation increase on HIC1 Lysine314 favors the direct transcriptional repression of SIRT1 and thus the P53-dependent apoptotic response to irreparable DNA double strand breaks (DSBs). HIC1 is also essential for DSBs repair but in a SUMOylation-independent manner. Here, we show that repairable DSBs induced by a 1 h Etoposide treatment results in three specific posttranslational modifications (PTMs) of HIC1. Two of these PTMs, phosphorylation of Serine 694 and Acetylation of Lysine 623 are located in the conserved HIC1 C-terminal region located downstream of the Zinc Finger DNA-binding domain. By contrast, phosphorylation of Serine 285 found in the poorly conserved central region is unique to the human protein. We showed that Ser694 phosphorylation is mediated mainly by the PIKK kinase ATM and is essential for the DNA repair activity of HIC1 as demonstrated by the lack of efficiency of the S694A point mutant in Comet assays. Thus, our results provide the first evidence for a functional role of the conserved HIC1 C-terminal region as a novel ATM substrate that plays an essential role in the cellular HIC1-mediated cellular response to repairable DSBs. |
| تدمد: | 1090-2104 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ee807591ea753ae2639bf76c2a12360eTest https://pubmed.ncbi.nlm.nih.gov/33756345Test |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....ee807591ea753ae2639bf76c2a12360e |
| قاعدة البيانات: | OpenAIRE |
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