dc.contributor.author | Day, Tovah A. | en_US |
dc.contributor.author | Layer, Jacob V. | en_US |
dc.contributor.author | Cleary, J. Patrick | en_US |
dc.contributor.author | Guha, Srijoy | en_US |
dc.contributor.author | Stevenson, Kristen E. | en_US |
dc.contributor.author | Tivey, Trevor | en_US |
dc.contributor.author | Kim, Sunhee | en_US |
dc.contributor.author | Schinzel, Anna C. | en_US |
dc.contributor.author | Izzo, Francesca | en_US |
dc.contributor.author | Doench, John | en_US |
dc.contributor.author | Root, David E. | en_US |
dc.contributor.author | Hahn, William C. | en_US |
dc.contributor.author | Price, Brendan D. | en_US |
dc.contributor.author | Weinstock, David M. | en_US |
dc.date.accessioned | 2017-06-15T18:29:53Z | |
dc.date.issued | 2017 | en_US |
dc.identifier.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. | en |
dc.identifier.issn | | en |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:33029857 | |
dc.description.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. | en |
dc.language.iso | en_US | en |
dc.publisher | Nature Publishing Group | en |
dc.relation.isversionof | doi:10.1038/ncomms15110 | en |
dc.relation.hasversion | http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5414184/pdf/ | en |
dash.license | LAA | en_US |
dc.title | PARP3 is a promoter of chromosomal rearrangements and limits G4 DNA | en |
dc.type | Journal Article | en_US |
dc.description.version | Version of Record | en |
dc.relation.journal | Nature Communications | en |
dash.depositing.author | Hahn, William C. | en_US |
dc.date.available | 2017-06-15T18:29:53Z | |
dc.identifier.doi | 10.1038/ncomms15110 | * |
dash.authorsordered | false | |
dash.contributor.affiliated | Price, Brendan | |
dash.contributor.affiliated | Hahn, William | |
dash.contributor.affiliated | Weinstock, David | |