scholarly journals A tunable zinc finger-based framework for Boolean logic computation in mammalian cells

2012 ◽  
Vol 40 (11) ◽  
pp. 5180-5187 ◽  
Author(s):  
Jason J. Lohmueller ◽  
Thomas Z. Armel ◽  
Pamela A. Silver
Keyword(s):  
Zinc Finger ◽  
Mammalian Cells ◽  
Boolean Logic ◽  
Logic Computation

scholarly journals COMET: A toolkit for composing customizable genetic programs in mammalian cells

2019 ◽  
Author(s):  
Patrick S. Donahue ◽  
Joseph W. Draut ◽  
Joseph J. Muldoon ◽  
Hailey I. Edelstein ◽  
Neda Bagheri ◽  
...  
Keyword(s):  
Gene Expression ◽  
Mathematical Model ◽  
Transcription Factors ◽  
Zinc Finger ◽  
Mammalian Cells ◽  
Single Layer ◽  
Performance Characteristics ◽  
Boolean Logic ◽  
Design And Construction

ABSTRACTEngineering mammalian cells to carry out sophisticated and customizable genetic programs requires a toolkit of multiple orthogonal and well-characterized transcription factors (TFs). To address this need, we developed the COmposable Mammalian Elements of Transcription (COMET)—an ensemble of TFs and promoters that enable the design and tuning of gene expression to an extent not previously possible. COMET currently comprises 44 activating and 12 inhibitory zinc-finger TFs and 83 cognate promoters, combined in a framework that readily accommodates new parts. This system can tune gene expression over three orders of magnitude, provides chemically inducible control of TF activity, and enables single-layer Boolean logic. We also develop a mathematical model that provides mechanistic insights into COMET performance characteristics. Altogether, COMET enables the design and construction of customizable genetic programs in mammalian cells.

Boolean Logic Tree of Label-Free Dual-Signal Electrochemical Aptasensor System for Biosensing, Three-State Logic Computation, and Keypad Lock Security Operation

2017 ◽  
Vol 89 (18) ◽  
pp. 9734-9741 ◽  
Author(s):  
Jiao Yang Lu ◽  
Xin Xing Zhang ◽  
Wei Tao Huang ◽  
Qiu Yan Zhu ◽  
Xue Zhi Ding ◽  
...  
Keyword(s):  
Boolean Logic ◽  
Label Free ◽  
Electrochemical Aptasensor ◽  
Logic Tree ◽  
Logic Computation

scholarly journals MORC2 regulates DNA damage response through a PARP1-dependent pathway

2019 ◽  
Vol 47 (16) ◽  
pp. 8502-8520 ◽  
Author(s):  
Lin Zhang ◽  
Da-Qiang Li
Keyword(s):  
Dna Damage ◽  
Zinc Finger ◽  
Chromatin Remodeling ◽  
Dna Damage Response ◽  
Mammalian Cells ◽  
Cellular Response ◽  
Genotoxic Stress ◽  
Underlying Mechanism ◽  
Dna Lesions ◽  
Damage Response

Abstract Microrchidia family CW-type zinc finger 2 (MORC2) is a newly identified chromatin remodeling enzyme with an emerging role in DNA damage response (DDR), but the underlying mechanism remains largely unknown. Here, we show that poly(ADP-ribose) polymerase 1 (PARP1), a key chromatin-associated enzyme responsible for the synthesis of poly(ADP-ribose) (PAR) polymers in mammalian cells, interacts with and PARylates MORC2 at two residues within its conserved CW-type zinc finger domain. Following DNA damage, PARP1 recruits MORC2 to DNA damage sites and catalyzes MORC2 PARylation, which stimulates its ATPase and chromatin remodeling activities. Mutation of PARylation residues in MORC2 results in reduced cell survival after DNA damage. MORC2, in turn, stabilizes PARP1 through enhancing acetyltransferase NAT10-mediated acetylation of PARP1 at lysine 949, which blocks its ubiquitination at the same residue and subsequent degradation by E3 ubiquitin ligase CHFR. Consequently, depletion of MORC2 or expression of an acetylation-defective PARP1 mutant impairs DNA damage-induced PAR production and PAR-dependent recruitment of DNA repair proteins to DNA lesions, leading to enhanced sensitivity to genotoxic stress. Collectively, these findings uncover a previously unrecognized mechanistic link between MORC2 and PARP1 in the regulation of cellular response to DNA damage.

scholarly journals APLF (C2orf13) Is a Novel Component of Poly(ADP-Ribose) Signaling in Mammalian Cells

2008 ◽  
Vol 28 (14) ◽  
pp. 4620-4628 ◽  
Author(s):  
Stuart L. Rulten ◽  
Felipe Cortes-Ledesma ◽  
Liandi Guo ◽  
Natasha J. Iles ◽  
Keith W. Caldecott
Keyword(s):  
Zinc Finger ◽  
Mammalian Cells ◽  
Strand Break ◽  
Zinc Finger Domain ◽  
Chromosomal Damage ◽  
Chromosomal Dna ◽  
Fha Domain ◽  
Break Repair ◽  
Dna Strand ◽  
Tandem Zinc Finger

ABSTRACT APLF is a novel protein of unknown function that accumulates at sites of chromosomal DNA strand breakage via forkhead-associated (FHA) domain-mediated interactions with XRCC1 and XRCC4. APLF can also accumulate at sites of chromosomal DNA strand breaks independently of the FHA domain via an unidentified mechanism that requires a highly conserved C-terminal tandem zinc finger domain. Here, we show that the zinc finger domain binds tightly to poly(ADP-ribose), a polymeric posttranslational modification synthesized transiently at sites of chromosomal damage to accelerate DNA strand break repair reactions. Protein poly(ADP-ribosyl)ation is tightly regulated and defects in either its synthesis or degradation slow global rates of chromosomal single-strand break repair. Interestingly, APLF negatively affects poly(ADP-ribosyl)ation in vitro, and this activity is dependent on its capacity to bind the polymer. In addition, transient overexpression in human A549 cells of full-length APLF or a C-terminal fragment encoding the tandem zinc finger domain greatly suppresses the appearance of poly(ADP-ribose), in a zinc finger-dependent manner. We conclude that APLF can accumulate at sites of chromosomal damage via zinc finger-mediated binding to poly(ADP-ribose) and is a novel component of poly(ADP-ribose) signaling in mammalian cells.

scholarly journals Author Correction: Synthetic RNA-based logic computation in mammalian cells

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Satoshi Matsuura ◽  
Hiroki Ono ◽  
Shunsuke Kawasaki ◽  
Yi Kuang ◽  
Yoshihiko Fujita ◽  
...  
Keyword(s):  
Mammalian Cells ◽  
Logic Computation
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