RT Journal Article
SR Electronic
T1 Parp3 promotes long-range end-joining in murine cells
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 255281
DO 10.1101/255281
A1 Jacob V. Layer
A1 J. Patrick Cleary
A1 Alexander J. Brown
A1 Kristen E. Stevenson
A1 Sara N. Morrow
A1 Alexandria Van Scoyk
A1 Rafael B. Blasco
A1 Elif Karaca
A1 Fei-Long Meng
A1 Richard L. Frock
A1 Trevor Tivey
A1 Sunhee Kim
A1 Hailey Fuchs
A1 Roberto Chiarle
A1 Frederick W. Alt
A1 Steven A. Roberts
A1 David M. Weinstock
A1 Tovah A. Day
YR 2018
UL http://biorxiv.org/content/early/2018/01/28/255281.abstract
AB Chromosomal rearrangements, including translocations, are early and essential events in the formation of many tumors. Previous studies that defined the genetic requirements for rearrangement formation have identified differences between murine and human cells, most notably in the role of classical‐ and alternative-nonhomologous end joining factors (NHEJ). We reported that poly(ADP)ribose polymerase 3 (PARP3) promotes chromosomal rearrangements induced by endonucleases in multiple human cell types. In contrast to c-NHEJ factors, we show here that Parp3 also promotes rearrangements in murine cells, including translocations in murine embryonic stem cells (mESCs), class switch recombination in primary B cells and inversions in tail fibroblasts that generate Eml4-Alk fusions. In mESCs, Parp3-deficient cells had shorter deletion lengths at translocation junctions. This was corroborated using next-generation sequencing of Eml4-Alk junctions in tail fibroblasts and is consistent with a role for Parp3 in promoting the processing of DNA double-strand breaks. We confirmed a previous report that Parp1 also promotes rearrangement formation. In contrast with Parp3, rearrangement junctions in the absence of Parp1 had longer deletion lengths, suggesting Parp1 may suppress DSB processing. Together, these data indicate that Parp3 and Parp1 promote rearrangements with distinct phenotypes.