REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
Anti-uN2CpolyG (SVEMAMNPV), Mouse Monoclonal Clone 4C4	This paper	N/A
Anti-uN2CpolyG (AARPPRMH), Mouse Monoclonal Clone 4D12	This paper	N/A
Anti-FLAG (DYKDDDDK) tag, Rabbit Polyclonal,	Thermo Fisher Scientific	Cat# PA1-984B; RRID: AB_347227
Anti-HA (YPYDVPDYA) tag, Mouse Monoclonal Clone 16B12	Abcam	Cat# ab130275; RRID: AB_11156884
Anti-GFP, Rabbit Polyclonal,	Abcam	Cat# ab290; RRID: AB_303395
Anti-GAPDH, Mouse Monoclonal Clone GA1R	Abcam	Cat# ab125247; RRID: AB_11129118
Anti-Calbindin, Mouse Monoclonal Clone CB-955	Abcam	Cat# ab82812; RRID: AB_1658451
Anti-Ubiquitin, Rabbit Monoclonal Recombinant EPR8830	Abcam	Cat# ab134953; RRID: AB_2801561
Anti-Sumo 2 and 3, Rabbit Polyclonal	Abcam	Cat# ab3742; RRID: AB_304041
Anti-p62 (SQSTM1), Rabbit Monoclonal Recombinant EPR4844	Abcam	Cat# ab109012; RRID: AB_2810880
Anti-MAP2, Mouse Monoclonal Clone MT-01	Abcam	Cat# ab7756; RRID: AB_306050
Anti-Histone H2A.X phospho S139, Rabbit Monoclonal Recombinant EP854(2)Y	Abcam	Cat# ab81299; RRID: AB_1640564
Anti-Histone H2A.X, Rabbit Monoclonal Recombinant EPR22820-23	Abcam	Cat# ab229914
Anti-Ku80 (XRCC5), Mouse Monoclonal Clone 5C5	Abcam	Cat# ab119935; RRID: AB_10899161
Anti-Ku-70 (XRCC6), Mouse Monoclonal Clone N3H10	Santa Cruz Biotechnology	Cat# sc-56129; RRID: AB_794205
Anti-GFAP, Rabbit Polyclonal,	Proteintech	Cat# 16825-1-AP; RRID: AB_2109646
Bacterial and virus strains
AAV2/PHP.eB CAG GFP	This paper	N/A
AAV2/PHP.eB CAG uN2C-GFP	This paper	N/A
AAV2/PHP.eB CAG uN2CpolyG-GFP	This paper	N/A
One Shot Stbl3 Chemically Competent E. coli	Invitrogen	Cat# C737303
One Shot TOP10 Chemically Competent E. coli	Invitrogen	Cat# C404003
Biological samples
Human skin and brain tissues	Described in Table S1	N/A
Chemicals, peptides, and recombinant proteins
Lysostaphin Enzyme Protein Recombinant	ProSpec	Cat# ENZ-269
Histosol Plus	LifeScience Products	Cat# HS-100-5GL
TO-PRO-3 Iodide (642/661) - 1 mM Solution in DMSO	Fisher Scientific	Cat# T-3605
Lipofectamine 2000 Transfection reagent	Fisher Scientific	Cat# 11668019
Complete Mini EDTA-free Protease Inhibitor Cocktail	Roche	Cat# 11836170001
Bafilomycin A1	Sigma	Cat# B1793
MG132	Sigma	Cat# M8699
Doxycycline hydrochloride	Sigma	Cat# D3447
Critical commercial assays
Anti-GFP Magnetic beads	Abcam	Cat# ab193983
Anti-HA Magnetic Beads	Pierce	Cat# 88837
EC Prime Western Blotting Detection Reagent	Sigma	Cat# GERPN2236
DAB Substrate Kit	Abcam	Cat# ab64238
TRI Reagent (Guanidine Thiocyanate & Phenol)	Merck	Cat# T9424-25ML
Transcriptor High Fidelity cDNA Synthesis Kit	Sigma	Cat# 5081955001
LightCycler 480 SYBR Green I Master	Roche	Cat# 04707516001
Experimental models: Cell lines
Human: U2OS cells	ATCC	Cat# 300364/p489_U-2_OS; RRID: CVCL_0042
Human: HEK293 cells	ATCC	Cat# 300192/p777_HEK293; RRID: CVCL_0045
Mouse: GT1-7 cells	ATCC	Cat# SCC116; RRID: CVCL_0281
Human: U2OS T-REx TO-uN2C-GFP	This paper	N/A
Human: U2OS T-REx TO-uN2CpolyG-GFP	This paper	N/A
Experimental models: Organisms/strains
Wild type Mouse: C57BL/6J Mus musculus	The Jackson, Laboratory	JAX:000664, RRID: IMSR_JAX:000664
Oligonucleotides
Primer RT-qPCR GFP Forward ACGTAAACGGCCACAAGTTC	This paper	N/A
Primer RT-qPCR GFP Reverse AAGTCGTGCTGCTTCATGTG	This paper	N/A
Primer RT-qPCR RPLP0 Forward GAAGTCACTGTGCCAGCCCA	This paper	N/A
Primer RT-qPCR RPLP0 Reverse GAAGGTGTAATCCGTCTCCA	This paper	N/A
Recombinant DNA
Plasmid: pcDNA3-TetOn uN2C-GFP (12 GLY)	This paper	N/A
Plasmid: pcDNA3-TetOn uN2CpolyG-GFP (100 GLY)	This paper	N/A
Plasmid: pAAV2-CAG uN2C-GFP (12 GLY)	This paper	N/A
Plasmid: pAAV2-CAG uN2CpolyG-GFP (100 GLY)	This paper	N/A
Plasmid: pcDNA3 NOTCH2NLC Exon1-GFP Gly frame	This paper	N/A
Plasmid: pcDNA3 NOTCH2NLC Exon1-GFP Ala frame	This paper	N/A
Plasmid: pcDNA3 NOTCH2NLC Exon1-GFP Arg frame	This paper	N/A
Plasmid: pcDNA3 ATG GLY 70x-GFP	This paper	N/A
Plasmid: pcDNA3 ATG ALA 100x-GFP	This paper	N/A
Plasmid: pcDNA3 ATG ARG 100x-GFP	This paper	N/A
Software and algorithms
Fiji (ImageJ)	NIH	RRID: SCR_002285
Prism	GraphPad	RRID: SCR_005375