PARP3 is a promoter of chromosomal rearrangements and limits G4 DNA

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PARP3 is a promoter of chromosomal rearrangements and limits G4 DNA

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Title: PARP3 is a promoter of chromosomal rearrangements and limits G4 DNA
Author: Day, Tovah A.; Layer, Jacob V.; Cleary, J. Patrick; Guha, Srijoy; Stevenson, Kristen E.; Tivey, Trevor; Kim, Sunhee; Schinzel, Anna C.; Izzo, Francesca; Doench, John; Root, David E.; Hahn, William C.; Price, Brendan D.; Weinstock, David M.

Note: Order does not necessarily reflect citation order of authors.

Citation: Day, T. A., J. V. Layer, J. P. Cleary, S. Guha, K. E. Stevenson, T. Tivey, S. Kim, et al. 2017. “PARP3 is a promoter of chromosomal rearrangements and limits G4 DNA.” Nature Communications 8 (1): 15110. doi:10.1038/ncomms15110. http://dx.doi.org/10.1038/ncomms15110.
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Abstract: 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.
Published Version: doi:10.1038/ncomms15110
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5414184/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:33029857
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