Tovah A. Day
Clark University
DNA damageMolecular biologyGeneticsBiologyCell biology
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Publications 14
#1Hongyun Qi (Harvard University)H-Index: 1
#2Brendan D. Price (Harvard University)H-Index: 42
Last. Tovah A. Day (Clark University)H-Index: 7
view all 3 authors...
Although stress-induced synthesis of mono(ADP-ribose) (mADPr) and poly(ADP-ribose) (pADPr) conjugates by pADPr polymerase (PARP) enzymes has been studied extensively, the removal and degradation of pADPr, as well as the fate of ADPr metabolites, have received less attention. The observations that stress-induced pADPr undergoes rapid turnover, and that deficiencies in ADPr degradation phenocopy loss of pADPr synthesis, suggest that ADPr degradation is fundamentally important to the cellular stres...
2 CitationsSource
#1Jacob V. Layer (Harvard University)H-Index: 3
#2J. Patrick Cleary (Harvard University)H-Index: 2
Last. Tovah A. Day (Harvard University)H-Index: 7
view all 18 authors...
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 classic and alternative nonhomologous end-joining (NHEJ) factors. We reported that poly(ADP)ribose polymerase 3 (PARP3) promotes chromosomal rearrangements induced by endonucleases in multiple human cell types. ...
2 CitationsSource
#1Tovah A. DayH-Index: 7
#2Jacob V. LayerH-Index: 3
Last. David M. WeinstockH-Index: 44
view all 14 authors...
Nature Communications 8: Article number: 15110 (2017); Published: 27 Apr 2017; Updated: 13 Jun 2017 In this Article, the antibody ‘BG4’ is consistently referred to incorrectly as ‘hf2’. These errors appear in the Results and Methods. Additionally, the Article incorrectly cites reference 52 in the sentences ‘A recent study described hf2, an engineered single-chain antibody specific for G4 DNA52’ and ‘pSANG10-3F-BG4 (Addgene 55756)52 was transformed into….
#1Tovah A. Day (Harvard University)H-Index: 7
#2Jacob V. Layer (Harvard University)H-Index: 3
Last. David M. Weinstock (Harvard University)H-Index: 44
view all 14 authors...
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 ...
12 CitationsSource
#1Young Eun Choi (Harvard University)H-Index: 10
#2Khyati Meghani (Harvard University)H-Index: 6
Last. Dipanjan Chowdhury (Harvard University)H-Index: 35
view all 15 authors...
High-grade serous ovarian carcinomas (HGSOCs) with BRCA1/2 mutations exhibit improved outcome and sensitivity to double-strand DNA break (DSB)-inducing agents (i.e., platinum and poly(ADP-ribose) polymerase inhibitors [PARPis]) due to an underlying defect in homologous recombination (HR). However, resistance to platinum and PARPis represents a significant barrier to the long-term survival of these patients. Although BRCA1/2-reversion mutations are a clinically validated resistance mechanism, the...
30 CitationsSource
#1Andrew A. Lane (Harvard University)H-Index: 23
#2Bjoern Chapuy (Harvard University)H-Index: 33
Last. David M. Weinstock (Harvard University)H-Index: 44
view all 31 authors...
Our goal is to identify oncogenic loci in regions of recurrent DNA copy number alterations in cancer. Constitutional trisomy 21 (Down syndrome) carries a 20-fold increased risk of B-ALL, and chr.21 gains are the most common acquired aneuploidy in B-ALL. Interstitial amplification in the chr.21q22 region (iAMP21) is also a recurrent finding in B-ALL and carries a poor prognosis. However, the gene(s) on chr.21 responsible for this association remain unclear. We studied the Ts1Rhr mouse, which carr...
1 CitationsSource
#1Andrew A. Lane (Harvard University)H-Index: 23
#2Bjoern Chapuy (Harvard University)H-Index: 33
Last. David M. Weinstock (Broad Institute)H-Index: 44
view all 31 authors...
David Weinstock and colleagues identify a triplication at chromosome 21q22 that is associated with development of B cell acute lymphoblastic leukemia (B-ALL) that causes B cell self renewal in vitro. They further demonstrate that this triplication leads to overexpression of the nucleosome remodeling protein HMGN1 and loss of H3K27me3, implicating these changes in B-ALL.
56 CitationsSource
#1Andrew A. Lane (Harvard University)H-Index: 23
#2Diederik van Bodegom (Harvard University)H-Index: 8
Last. David M. Weinstock (Harvard University)H-Index: 44
view all 11 authors...
Abstract 115 Extra copies of chromosome 21 (polysomy 21) is the most common somatic aneuploidy in B-cell acute lymphoblastic leukemia (B-ALL), including >90% of cases with high hyperdiploidy. In addition, children with Down syndrome (DS) have a 20-fold increased risk of developing B-ALL, of which ∼60% harbor CRLF2 rearrangements. To examine these associations within genetically defined models, we investigated B-lineage phenotypes in Ts1Rhr mice, which harbor triplication of 31 genes syntenic wit...
#1Chaitali Dutta (Harvard University)H-Index: 5
#2Tovah A. Day (Harvard University)H-Index: 7
Last. David M. Weinstock (Harvard University)H-Index: 44
view all 15 authors...
BCL2 suppresses apoptosis by binding the BH3 domain of proapoptotic factors and thereby regulating outer mitochondrial membrane permeabilization. Many tumor types, including B-cell lymphomas and chronic lymphocytic leukemia, are dependent on BCL2 for survival but become resistant to apoptosis after treatment. Here, we identified a direct interaction between the antiapoptotic protein BCL2 and the enzyme PARP1, which suppresses PARP1 enzymatic activity and inhibits PARP1-dependent DNA repair in di...
23 CitationsSource
#1Laura R. Barkley (National University of Ireland, Galway)H-Index: 7
#2Komaraiah Palle (UNC: University of North Carolina at Chapel Hill)H-Index: 3
Last. Cyrus Vaziri (UNC: University of North Carolina at Chapel Hill)H-Index: 31
view all 9 authors...
The E3 ubiquitin ligase Rad18 chaperones DNA polymerase η (Polη) to sites of UV-induced DNA damage and monoubiquitinates proliferating cell nuclear antigen (PCNA), facilitating engagement of Polη with stalled replication forks and promoting translesion synthesis (TLS). It is unclear how Rad18 activities are coordinated with other elements of the DNA damage response. We show here that Ser-409 residing in the Polη-binding motif of Rad18 is phosphorylated in a checkpoint kinase 1–dependent manner i...
15 CitationsSource