Waaqo Daddacha
Emory University
DNA repairMolecular biologySIRT2Cancer researchBiology
What is this?
Publications 8
#1PamelaSara E. Head (Emory University)H-Index: 4
#2Nagaraju P. Ganji (Emory University)
Last. David S. Yu (Emory University)H-Index: 20
view all 15 authors...
DNA-dependent protein kinase (DNA-PK) plays a critical role in non-homologous end joining (NHEJ), the predominant pathway that repairs DNA double-strand breaks (DSB) in response to ionizing radiation (IR) to govern genome integrity. How DNA-PK is activated in response to DSBs has remained elusive. Here, we show that the SIRT2 sirtuin deacetylase and tumor suppressor directs the activation of DNA-PK through deacetylation of its catalytic subunit (DNA-PKcs). SIRT2 deacetylase activity governs cell...
#1Ashley J. Schlafstein (Emory University)H-Index: 1
#2Allison E. Withers (Emory University)H-Index: 2
Last. David S. Yu (Emory University)H-Index: 20
view all 13 authors...
Failure to achieve pathologic complete response is associated with poor prognosis in breast cancer patients following neoadjuvant chemotherapy (NACT). However, prognostic biomarkers for clinical outcome are unclear in this patient population. Cyclin-dependent kinase 9 (CDK9) is often dysregulated in breast cancer, and its deficiency results in genomic instability. We reviewed the records of 84 breast cancer patients from Emory University’s Winship Cancer Institute who had undergone surgical rese...
1 CitationsSource
#1David S. YuH-Index: 20
#2Waaqo DaddachaH-Index: 3
Last. Baek KimH-Index: 35
view all 25 authors...
#1Allyson E. Koyen (Emory University)H-Index: 3
#2Geraldine N. Nabeta (Emory University)H-Index: 1
Last. Waaqo Daddacha (Emory University)H-Index: 3
view all 6 authors...
Protein kinases play a vital role in the regulation of pathways that control cell growth, proliferation, survival, and differentiation. Epidermal growth factor receptor (EGFR) is a key protein kinase that when dysregulated, disrupts these pathways and, accordingly, is associated with several cancers. Thus, EGFR has been a focus of investigation as a therapeutic target for cancer treatment for the past several decades, with fair success. Despite this success, EGFR-targeted therapies are not unive...
#1Waaqo Daddacha (Emory University)H-Index: 3
#2Allyson E. Koyen (Emory University)H-Index: 3
Last. David S. Yu (Emory University)H-Index: 20
view all 28 authors...
Summary DNA double-strand break (DSB) repair by homologous recombination (HR) is initiated by CtIP/MRN-mediated DNA end resection to maintain genome integrity. SAMHD1 is a dNTP triphosphohydrolase, which restricts HIV-1 infection, and mutations are associated with Aicardi-Goutieres syndrome and cancer. We show that SAMHD1 has a dNTPase-independent function in promoting DNA end resection to facilitate DSB repair by HR. SAMHD1 deficiency or Vpx-mediated degradation causes hypersensitivity to DSB-i...
33 CitationsSource
#1PamelaSara E. Head (Emory University)H-Index: 4
#2Hui Zhang (Emory University)H-Index: 9
Last. David S. Yu (Emory University)H-Index: 20
view all 8 authors...
Abstract Sirtuin 2 (SIRT2) is a sirtuin family deacetylase, which maintains genome integrity and prevents tumorigenesis. Although Sirt2 deficiency in mice leads to tumorigenesis, the functional significance of somatic SIRT2 mutations in human tumors is unclear. Using structural insight combined with bioinformatics and functional analyses, we show that naturally occurring cancer-associated SIRT2 mutations at evolutionarily conserved sites disrupt its deacetylation of DNA-damage response proteins ...
8 CitationsSource
#1Waaqo Daddacha (Emory University)H-Index: 3
#2Allyson E. Koyen (Emory University)H-Index: 3
Last. David S. Yu (Emory University)H-Index: 20
view all 4 authors...
STAT3 is a member of the signal transducer and activator of transcription (STAT) family of proteins. Activation of the STAT3 signaling cascade results in the transcription of several pro-proliferative and anti-apoptotic proteins. STAT3 is also a potent modulator of the immune system, and its activation results in the suppression of the immune response. Dysregulation of STAT3 is implicated in the development and progression of a number of malignancies, including pancreatic ductal adenocarcinoma. ...
#1Hui Zhang (Emory University)H-Index: 9
#2Pamela Sara E. Head (Emory University)H-Index: 1
Last. David S. Yu (Emory University)H-Index: 20
view all 23 authors...
The ataxia telangiectasia-mutated and Rad3-related (ATR) kinase checkpoint pathway maintains genome integrity; however, the role of the sirtuin 2 (SIRT2) acetylome in regulating this pathway is not clear. We found that deacetylation of ATR-interacting protein (ATRIP), a regulatory partner of ATR, by SIRT2 potentiates the ATR checkpoint. SIRT2 interacts with and deacetylates ATRIP at lysine 32 (K32) in response to replication stress. SIRT2 deacetylation of ATRIP at K32 drives ATR autophosphorylat...
20 CitationsSource