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Tom Ellenberger
Washington University in St. Louis
34Publications
17H-index
1,622Citations
Publications 34
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#1Jamie R. Wallen (WCU: Western Carolina University)H-Index: 1
#2Hao F. Zhang (WashU: Washington University in St. Louis)H-Index: 44
Last.Tom Ellenberger (WashU: Washington University in St. Louis)H-Index: 17
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Summary The physical organization of DNA enzymes at a replication fork enables efficient copying of two antiparallel DNA strands, yet dynamic protein interactions within the replication complex complicate replisome structural studies. We employed a combination of crystallographic, native mass spectrometry and small-angle X-ray scattering experiments to capture alternative structures of a model replication system encoded by bacteriophage T7. Two molecules of DNA polymerase bind the ring-shaped pr...
8 CitationsSource
#1Chris A. Brosey (WashU: Washington University in St. Louis)H-Index: 7
#2Chris M. W. Ho (WashU: Washington University in St. Louis)H-Index: 8
Last.John A. Tainer (LBNL: Lawrence Berkeley National Laboratory)H-Index: 106
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Summary Apoptosis-inducing factor (AIF) is critical for mitochondrial respiratory complex biogenesis and for mediating necroptotic parthanatos; these functions are seemingly regulated by enigmatic allosteric switching driven by NADH charge-transfer complex (CTC) formation. Here, we define molecular pathways linking AIF's active site to allosteric switching regions by characterizing dimer-permissive mutants using small-angle X-ray scattering (SAXS) and crystallography and by probing AIF-CTC commu...
10 CitationsSource
#1Abigael Cheruiyot (WashU: Washington University in St. Louis)H-Index: 2
#2Sharad C. Paudyal (WashU: Washington University in St. Louis)H-Index: 5
Last.Zhongsheng You (WashU: Washington University in St. Louis)H-Index: 19
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Abstract Exonuclease 1 (Exo1) has important roles in DNA metabolic transactions that are essential for genome maintenance, telomere regulation and cancer suppression. However, the mechanisms for regulating Exo1 activity in these processes remain incompletely understood. Here, we report that Exo1 activity is regulated by a direct interaction with poly(ADP-ribose) (PAR), a prominent posttranslational modification at the sites of DNA damage. This PAR-binding activity promotes the early recruitment ...
9 CitationsSource
#1Vandna Kukshal (WashU: Washington University in St. Louis)H-Index: 6
#2In-Kwon Kim (WashU: Washington University in St. Louis)H-Index: 11
Last.Tom Ellenberger (WashU: Washington University in St. Louis)H-Index: 17
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Mammalian DNA ligase III (LigIII) functions in both nuclear and mitochondrial DNA metabolism. In the nucleus, LigIII has functional redundancy with DNA ligase I whereas LigIII is the only mitochondrial DNA ligase and is essential for the survival of cells dependent upon oxidative respiration. The unique LigIII zinc finger (ZnF) domain is not required for catalytic activity but senses DNA strand breaks and stimulates intermolecular ligation of two DNAs by an unknown mechanism. Consistent with thi...
13 CitationsSource
#1John M. Pascal (Thomas Jefferson University)H-Index: 29
#2Tom Ellenberger (WashU: Washington University in St. Louis)H-Index: 17
Human cells respond to DNA damage with an acute and transient burst in production of poly(ADP-ribose), a posttranslational modification that expedites damage repair and plays a pivotal role in cell fate decisions. Poly(ADP-ribose) polymerases (PARPs) and glycohydrolase (PARG) are the key set of enzymes that orchestrate the rise and fall in cellular levels of poly(ADP-ribose). In this perspective, we focus on recent structural and mechanistic insights into the enzymes involved in poly(ADP-ribose)...
36 CitationsSource
#1Xiaoqing Chen (WashU: Washington University in St. Louis)H-Index: 2
#2In-Kwon Kim (WashU: Washington University in St. Louis)H-Index: 11
Last.Zhongsheng You (WashU: Washington University in St. Louis)H-Index: 19
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The DNA end resection process dictates the cellular response to DNA double strand break damage and is essential for genome maintenance. Although insufficient DNA resection hinders homology-directed repair and ATR (ataxia telangiectasia and Rad3 related)-dependent checkpoint activation, overresection produces excessive single-stranded DNA that could lead to genomic instability. However, the mechanisms controlling DNA end resection are poorly understood. Here we show that the major resection nucle...
10 CitationsSource
#1Fiorella Ghisays (WashU: Washington University in St. Louis)H-Index: 1
#2Cynthia S. Brace (WashU: Washington University in St. Louis)H-Index: 6
Last.Tom Ellenberger (WashU: Washington University in St. Louis)H-Index: 17
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Summary The NAD + -dependent protein deacetylase SIRT1 regulates energy metabolism, responses to stress, and aging by deacetylating many different proteins, including histones and transcription factors. The mechanisms controlling SIRT1 enzymatic activity are complex and incompletely characterized, yet essential for understanding how to develop therapeutics that target SIRT1. Here, we demonstrate that the N-terminal domain of SIRT1 (NTERM) can trans-activate deacetylation activity by physically i...
24 CitationsSource
#1In-Kwon Kim (WashU: Washington University in St. Louis)H-Index: 11
#2Roderick A. Stegeman (WashU: Washington University in St. Louis)H-Index: 3
Last.Tom Ellenberger (WashU: Washington University in St. Louis)H-Index: 17
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The posttranslational modification of proteins with poly(ADP-ribose) (PAR) regulates protein-protein interactions in DNA repair, gene expression, chromatin structure, and cell fate determination. The PAR polymerase PARP1 binds to damaged chromatin and synthesizes PAR chains to signal DNA damage and recruit the DNA repair scaffold, XRCC1. Pharmacological blockade of PARP1 enzymatic activity impairs XRCC1-dependent repair of DNA damage and selectively kills cancer cells lacking other DNA repair fu...
22 CitationsSource
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