PARP3 is a promoter of chromosomal rearrangements and limits G4 DNA
| العنوان: | PARP3 is a promoter of chromosomal rearrangements and limits G4 DNA |
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| المؤلفون: | William C. Hahn, David E. Root, Anna C. Schinzel, J. Patrick Cleary, David M. Weinstock, Brendan D. Price, Srijoy Guha, John G. Doench, Jacob V. Layer, Tovah A. Day, Trevor Tivey, Kristen E. Stevenson, Sunhee Kim, Francesca Izzo |
| المصدر: | Nature Communications, Vol 8, Iss 1, Pp 1-15 (2017) Nature Communications |
| بيانات النشر: | Nature Portfolio, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | 0301 basic medicine, Multidisciplinary, biology, DNA damage, DNA repair, Poly ADP ribose polymerase, Science, General Physics and Astronomy, General Chemistry, Molecular biology, Article, General Biochemistry, Genetics and Molecular Biology, DNA End-Joining Repair, 03 medical and health sciences, chemistry.chemical_compound, 030104 developmental biology, chemistry, Rad50, biology.protein, Homologous recombination, Polymerase, DNA |
| الوصف: | Chromosomal rearrangements are essential events in the pathogenesis of both malignant and nonmalignant disorders, yet the factors affecting their formation are incompletely understood. Here we develop a zinc-finger nuclease translocation reporter and screen for factors that modulate rearrangements in human cells. We identify UBC9 and RAD50 as suppressors and 53BP1, DDB1 and poly(ADP)ribose polymerase 3 (PARP3) as promoters of chromosomal rearrangements across human cell types. We focus on PARP3 as it is dispensable for murine viability and has druggable catalytic activity. We find that PARP3 regulates G quadruplex (G4) DNA in response to DNA damage, which suppresses repair by nonhomologous end-joining and homologous recombination. Chemical stabilization of G4 DNA in PARP3−/− cells leads to widespread DNA double-strand breaks and synthetic lethality. We propose a model in which PARP3 suppresses G4 DNA and facilitates DNA repair by multiple pathways. Chromosomal rearrangements are key events in the pathogenesis of a range of disorders. Here the authors utilize a zinc finger nuclease translocation reporter to identify PARP3 as a regulator of these events at sites enriched for G quadruplex DNA. |
| اللغة: | English |
| تدمد: | 2041-1723 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1bf539731a508d815dd4c40eb87c6bbaTest https://doaj.org/article/bbb73c46fe524682b8101ab1da9d52fcTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....1bf539731a508d815dd4c40eb87c6bba |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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