REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
Mono- & polyubiquitinylated conjugates (FK2)	Enzo Life Sciences	BML-PW8810 RRID: AB_10541840
Mouse monoclonal anti-Pol II (A-10)	Santa Cruz Biotechnology	Cat#sc-17798; RRID: AB_677355
Mouse monoclonal anti-Pol II (F-12)	Santa Cruz Biotechnology	Cat#sc-55492 RRID: AB_630203
Rabbit monoclonal anti-MYC (clone Y69)	Abcam	Cat# ab32072 RRID: AB_731658
Mouse Monoclonal anti-MYC (C33)	Santa Cruz Biotechnology	Cat#sc-42 RRID: AB_2282408
Rabbit polyclonal anti-phospho-Ser2-RNAPII	Abcam	Cat# ab5095 RRID: AB_304749
Mouse monoclonal anti-RNAPII	MBL International	Cat# MABI0601 RRID: AB_2728735
Rabbit polyclonal anti-Histone H2B antibody	Abcam	Ab1790 RRID: AB_302612
Rabbit polyclonal anti-HUWE1/Mule antibody	Abcam	Ab70161 RRID: AB_1209511
Rabbit polyclonal anti-CTR9	Novus Biologicals	NB100-68205 RRID: AB_11002327
Rabbit polyclonal anti-CTR9	Bethyl Laboratories	A301-395 RRID: AB_960973
Rabbit polyclonal anti-Parafibromin (CDC73)	Bethyl Laboratories	A300-171A RRID: AB_2078660
Rabbit polyclonal anti-PAF1	Abcam	Ab20662 RRID: AB_2159769
Rabbit polyclonal anti-LEO1	Novus Biologicals	NB600-276 RRID: AB_2281237
Goat polyclonal anti-GST	GE Healthcare/Sigma- Aldrich	Cat#GE27-4577-01; Lot: 362611
Rabbit monoclonall Ubiquityl-Histone H2B (Lys120) (D11) XP®	Cell Signaling Technology	Cat#5546 RRID: AB_10693452
Mouse monoclonal anti-VCL	Sigma-Aldrich	Cat#V9131 RRID: AB_477629
Mouse monoclonal anti-phospho-Ser5-RNAPII	Biolegend	Cat#904001 RRID: AB_2565036
Rabbit polyclonal anti- CDK2	Santa Cruz Biotechnology	Cat#sc-163 RRID: AB_631215
Rabbit polyclonal anti-CHK1(FL-476)	Santa Cruz Biotechnology	Cat#sc-7898 RRID: AB_2229488
Rabbit polyclonal anti-phospho-Chk1 (Ser345) (133D3)	Cell Signaling Technology	Cat#2348 RRID: AB_331212
Rabbit polyclonal anti- phospho-Histone H2A.X (Ser 139)	Cell Signaling Technology	Cat#2577 RRID: AB_2118010
Rabbit polyclonal anti-KAP1 (phospho S824)	Abcam	Cat#ab70369 RRID: AB_1209417
Rabbit polyclonal anti- KAP1	Bethyl Laboratories	Cat#A300-274A RRID: AB_185559
Rabbit monoclonall Anti-TH1L (D5G6W) (NELFC)	Cell Signaling Technology	Cat#12265S Lot:1 RRID: AB_2797862
Mouse monoclonal FITC anti-BrdU (clone 3D4)	Biozol / BioLegend	Cat#364104 RRID: AB_2564481
Donkey polyclonal anti-goat IgG-HRP secondary antibody	Santa Cruz Biotechnology	Cat#sc-2020 RRID: AB_631728
ECL-Anti-rabbit IgG Horseradish Peroxidase	GE Healthcare / Fisher Scientific GmbH	Cat#1079-4347 / GEHENA934
ECL-Anti-mouse IgG Horseradish Peroxidase	GE Healthcare / Fisher Scientific GmbH	Cat#1019-6124 / GEHENA931
IRDye 800CW Donkey anti-Rabbit IgG (H + L)	LI-COR Biosciences	Cat#926-32213 RRID: AB_621848
IRDye 680RD Donkey anti-Mouse IgG (H + L)	LI-COR Biosciences	Cat#926-68072 RRID: AB_10953628
Goat anti-Mouse IgG (H+L) Highly Cross-Adsorbed Secondary Antibody, Alexa Fluor 488	Thermo Fisher Scientific	Cat#A-11029 RRID: AB_138404
Goat anti-Mouse IgG (H+L) Highly Cross-Adsorbed Secondary Antibody, Alexa Fluor 568	Thermo Fisher Scientific	Cat#A-11004 RRID: AB_2534072
Bacterial and Virus Strains
pRRL-SFFV-IRES-Hygro	Wiese et al., 2015	N/A
pRRL-SFFV-MYC-IRES-Hygro	Wiese et al., 2015	N/A
pRRL-SFFV-OsTir1_3x_Myc_tag-T2A-eBFP2	Muhar et al., 2018	N/A
pInducer10 shCDC73-3	This paper	N/A
pInducer10 shCTR9-3	This paper	N/A
pGIPZ shCDC73-3	This paper	N/A
pGIPZ shCDC73-4	This paper	N/A
pGIPZ shCTR9-3	This paper	N/A
pGIPZ shCTR9-5	This paper	N/A
Chemicals, Peptides, and Recombinant Proteins
MG-132	Calbiochem / Merck	Cat#474790-20MG
HUWE1-Inhibitor BI8626	ProbeChem	N/A
Doxycycline hyclate	Sigma-Aldrich	Cat#D9891-10G
Indole-3-acetic acid sodium salt	Sigma-Aldrich	Cat# I5148-2G
Hoechst 33342	Sigma-Aldrich	Cat#B2261-25MG
5-Ethynyl-2'-deoxyuridine (5-EdU)	Jena Bioscience	Cat#CLK-N001-100
AF647-Picolyl-Azide	Jena Bioscience	Cat#CLK-1300-1
Lipofectamine RNAiMAX Transfection Reagent	Thermo Fischer Scientific	Cat#13778-150
Dynabeads Protein A	Thermo Fisher Scientific	Cat#10001D
Dynabeads Protein G	Thermo Fisher Scientific	Cat#10003D
Dynabeads® MyOne™ Streptavidin T1	Thermo Fisher Scientific	Cat#65601
Etoposide	Sigma-Aldrich	Cat#E1383
4-Hydroxytamoxifen	Sigma-Aldrich	Cat#H7904
Opti-MEM I	Thermo Fischer Scientific	Cat#31985-047
Propidium iodide	Sigma-Aldrich	Cat#81845
Protease inhibitor cocktail	Sigma-Aldrich	Cat#P8340
Phosphatase inhibitor cocktail 2	Sigma-Aldrich	Cat#P5726
Phosphatase inhibitor cocktail 3	Sigma-Aldrich	Cat#P0044
NuPAGE LDS Sample Buffer (4X)	Sigma-Aldrich	Cat#NP0007
Pierce™ DTT (Dithiothreitol), No-Weigh™ Format	Thermo Fisher Scientific	Cat#20291
Benzonase nuclease purity >99% 25U/μl	Merck Millipore	Cat#70664-3
InstantBlue(TM) Safe Coomassie Stain	Sigma-Aldrich	Cat#ISB1L-1L
Proteinase K	Roth	Cat#7528.2
RNase A	Roth	Cat#7156.1
16% Paraformaldehyde (Formaldehyde) Aqueous Solution, EM Grade	Science Services GmbH	Cat#E15710
Penicillin-Streptomycin	Sigma-Aldrich	Cat#P4333-100ML
HiMark pre-stained HMW STD	Thermo Fisher Scientific	Cat#LC5699
UltraPure BSA (50 mg/mL)	Thermo Fisher Scientific	Cat#AM2616
Polybrene	Sigma-Aldrich	Cat#H9268
Protamine sulfate	Sigma-Aldrich	Cat#P3369
Alexa Fluor568 Phalloidin	Thermo Fisher Scientific	Cat#A12380
N-Ethylmaleinimid	Sigma-Aldrich	Cat#E3876
Puromycin	InvivoGen	Cat#70664-3
Hygromycin B Gold solution	InvivoGen	Cat#ant-hg-05
Blasticidin	InvivoGen	Cat#ant-bl-05
CutSmart® Buffer	New England Biolabs	Cat#B7204S
T4 DNA Ligase Buffer	New England Biolabs	Cat#B0202S
Agencourt AMPure XP Beads	Beckman Coulter	Cat#A63881
Agencourt RNAClean XP Beads	Beckman Coulter	Cat#A63987
LDC4297	Selleckchem / Biozol	Cat#SEL-S7992
NVP-2	Tocris/Bio-Techne	Cat#6535/5
Odyssey Blocking Buffer in TBS	LI-COR Biosciences	Cat#927-50000
Glutathione Sepharose 4B	GE Healthcare / VWR International	Cat#17075601
L-Glutathion reduced, cell culture tested	Sigma-Aldrich	Cat#G6013-5G
Fugene	Promega	Cat#E2311
Critical Commercial Assays
Duolink In Situ PLA Probe Anti-Rabbit PLUS, Affinity purified Donkey anti-Rabbit IgG (H+L)	Sigma-Aldrich	Cat#DUO92002 RRID: AB_2810940
Duolink In Situ PLA Probe Anti-Mouse MINUS, Affinity purified Donkey anti-Mouse IgG (H+L)	Sigma-Aldrich	Cat#DUO92004 RRID: AB_2713942
Duolink In Situ Wash Buffers, Fluorescence	Sigma-Aldrich	Cat#DUO82049
Duolink In Situ Detection Reagents Green	Sigma-Aldrich	Cat#DUO92014
NGS Fragment High Sensitivity Analysis Kit, 1-6,000 bp, 500 samples	Agilent	DNF-474-0500
Standard Sensitivity RNA Analysis Kit (15nt), 500 samples	Agilent	DNF-471-0500
RNeasy Mini Kit	Qiagen	Cat#74106
MinElute PCR Purification Kit	Qiagen	Cat#28006
QIAquick PCR Purification Kit	Qiagen	Cat#28106
QIAquick Gel Extraction Kit	Qiagen	Cat#28704
NEBNext Ultra RNA Library Prep Kit for Illumina	New England Biolabs	Cat#E7530S
NEBNext Poly(A) mRNA Magnetic Isolation Modul	New England Biolabs	Cat#E7490L
NEBNext ChIP-Seq Prep Master Mix Set for Illumina	New England Biolabs	Cat#E6240S
NEBNext Ultra II DNA Library Prep	New England Biolabs	Cat# E7103L
NEBNext Multiplex Small RNA Library Prep Kit	New England Biolabs	Cat#E7560S
NextSeq 500/550 High Output Kit v2 (75cycles)	Illumina	FC-404-2005
Quant-iT Pico Green	Thermo Fischer Scientific	Cat#P7589
AsiSI	New England Biolabs	Cat# R0630
ABsolute QPCR Mix, SYBR Green, no ROX	Thermo Fischer Scientific	Cat#AB-1158/B
Quick Blunting Kit	New England Biolabs	Cat#E1201L
T4 DNA Ligase, conc.	New England Biolabs	Cat#M0202M
T4 RNA Ligase 2, truncated	New England Biolabs	Cat#M0242L
NEBNext High-Fidelity 2X PCR Master Mix	New England Biolabs	Cat#M0541L
MEGAscript T7 Transcription Kit	Thermo Fischer Scientific	Cat#AM1334
SuperScript III Reverse Transcriptase	Thermo Fischer Scientific	Cat#T18080044
RNaseOUT Recombinant Ribonuclease Inhibitor	Thermo Fischer Scientific	Cat#10777019
ON-TARGETplus Non-targeting Pool	Horizon Discovery Group	Cat#D-001810-10-50
ON-TARGETplus Set of Four siRNA Library- Human Ubiquitin Conjugation Subset 1	Dharmacon	GU-105615 Lot 11107
ON-TARGETplus Set of Four siRNA Library- Human Ubiquitin Conjugation Subset 2	Dharmacon	GU-105625 Lot 11108
ON-TARGETplus SMARTpool® siRNA Library - Human Ubiquitin Conjugation Subset 3	Dharmacon	GU-105635 Lot 11117
PTMScan Ubiquitin Remnant Motif (K-ε-GG) Kit	Cell Signaling Technology	Cat#5562
Deposited Data
Sequencing Data	This paper	GSE150217
Raw imaging data	This paper	10.17632/n4rr8ck4w 3.1
Experimental Models: Cell Lines
NIH 3T3	ATCC	CVCL_0594
U2OS	ATCC	N/A
HEK293TN	ATCC	CRT-11268
U2OS MYC-Tet-On	Walz et al., 2014	N/A
U2OS MYC-ER	Liu et al., 2012	N/A
K562 MYC-Aid	Muhar et al., 2018	N/A
Oligonucleotides
Primer ChIP_qPCR NCL_f CTACCACCCTCATCTGAATCC	Baluapuri et al., 2019	N/A
Primer ChIP qPCR NCL_r TTGTCTCGCTGGGAAAGG	Baluapuri et al., 2019	N/A
Primer ChIP qPCR NegReg_f TTTTCTCACATTGCCCCTGT	Baluapuri et al., 2019	N/A
Primer ChIP qPCR NegReg_r TCAATGCTGTACCAGGCAAA	Baluapuri et al., 2019	N/A
Primer ChIP qPCR GNL3 f GTGACGCTCGTCAGTGG	Jaenicke et al., 2016	N/A
Primer ChIP qPCR GNL3 r CATATTGGCTGTAGAAGG AAGC	Jaenicke et al., 2016	N/A
Primer ChIP qPCR NPM1 f TTCACCGGGAAGCATGG	Jaenicke et al., 2016	N/A
Primer ChIP qPCR NPM1 r CACGCGAGGTAAGTCTACG	Jaenicke et al., 2016	N/A
Primer ChIP qPCR IFRD1 r CGTGGTTTGGCTACTGAACT	This paper	N/A
Primer ChIP qPCR IFRD1 f CCTGTCCCGACACACTCTC	This paper	N/A
Primer ChIP qPCR CHMP2A r CAAGGTGGTGTTGGAGACCT	This paper	N/A
Primer ChIP qPCR CHMP2A f GGGGATCCCAGAAAGAGAAG	This paper	N/A
shCDC73 human mirE3 TGCTGTTGACAGTGAGCGCCAGCGATCTACTCAAG TCAAATAGTGAAGCCACAGATGTATTTGACTTGAGT AGATCGCTGATGCCTACTGCCTCGGA	Fellmann et al., 2013	N/A
shCDC73 human mirE4 TGCTGTTGACAGTGAGCGCCAGGTACATGGTAAAG CATAATAGTGAAGCCACAGATGTATTATGCTTTACC ATGTACCTGTTGCCTACTGCCTCGGA	Fellmann et al., 2013	N/A
shCTR9 human mirE3 TGCTGTTGACAGTGAGCGCTCGGATGAGGATAAAC TTAAATAGTGAAGCCACAGATGTATTTAAGTTTATCC TCATCCGAATGCCTACTGCCTCGGA	Fellmann et al., 2013	N/A
shCTR9 human mirE5 TGCTGTTGACAGTGAGCGAAAGCAACAAAAGAGAA GAAAATAGTGAAGCCACAGATGTATTTTCTTCTCTTT TGTTGCTTCTGCCTACTGCCTCGGA	Fellmann et al., 2013	N/A
MYC-f (pGex4T3) CCCGAATTCGCCCCTCAACGTTAGCTTC	Baluapuri et al., 2019	N/A
MYC-r (pGex4T3) GGGCTCGAGTCAGTTCGGGCTGCCGCTGTCT	Baluapuri et al., 2019	N/A
A1_Bottom [P]GCGTGATGNNNNNNNNGATCGTCGGACTGTAGA ACTCTGAACCCCTATAGTGAGTCGTATTACCGGCCT CAATCGAA	Yan et al., 2017	N/A
A1_Top CGATTGAGGCCGGTAATACGACTCACTATAGGGGT TCAGAGTTCTACAGTCCGACGATCNNNNNNNNCAT CACGC	Yan et al., 2017	N/A
A2_Bottom [P]GGAACGACNNNNNNNNGATCGTCGGACTGTAGA ACTCTGAACCCCTATAGTGAGTCGTATTACCGGCCT CAATCGAA	Yan et al., 2017	N/A
A2_Top CGATTGAGGCCGGTAATACGACTCACTATAGGGGT TCAGAGTTCTACAGTCCGACGATCNNNNNNNNGTC GTTCC	Yan et al., 2017	N/A
A3_Bottom [P]GATCATCANNNNNNNNGATCGTCGGACTGTAGAA CTCTGAACCCCTATAGTGAGTCGTATTACCGGCCTC AATCGAA	Yan et al., 2017	N/A
A3_Top CGATTGAGGCCGGTAATACGACTCACTATAGGGGT TCAGAGTTCTACAGTCCGACGATCNNNNNNNNTGAT GATC	Yan et al., 2017	N/A
A4_Bottom [P]GATGTCGTNNNNNNNNGATCGTCGGACTGTAGA ACTCTGAACCCCTATAGTGAGTCGTATTACCGGCCT CAATCGAA	Yan et al., 2017	N/A
A4_Top CGATTGAGGCCGGTAATACGACTCACTATAGGGGT TCAGAGTTCTACAGTCCGACGATCNNNNNNNNACG ACATC	Yan et al., 2017	N/A
A5_Bottom [P]GGATGATGNNNNNNNNGATCGTCGGACTGTAGA ACTCTGAACCCCTATAGTGAGTCGTATTACCGGCCT CAATCGAA	Yan et al., 2017	N/A
A5_Top CGATTGAGGCCGGTAATACGACTCACTATAGGGGT TCAGAGTTCTACAGTCCGACGATCNNNNNNNNCAT CATCC	Yan et al., 2017	N/A
A6_Bottom [P]GCGGTCGTNNNNNNNNGATCGTCGGACTGTAGA ACTCTGAACCCCTATAGTGAGTCGTATTACCGGCCT CAATCGAA	Yan et al., 2017	N/A
A6_Top CGATTGAGGCCGGTAATACGACTCACTATAGGGGT TCAGAGTTCTACAGTCCGACGATCNNNNNNNNACG ACCGC	Yan et al., 2017	N/A
RPI_01 CAAGCAGAAGACGGCATACGAGATCGAGTAATGTG ACTGGAGTTCCTTGGCACCCGAGAATTCCA	This paper	N/A
RPI_02 CAAGCAGAAGACGGCATACGAGATTCTCCGGAGTG ACTGGAGTTCCTTGGCACCCGAGAATTCCA	This paper	N/A
RPI_03 CAAGCAGAAGACGGCATACGAGATAATGAGCGGTG ACTGGAGTTCCTTGGCACCCGAGAATTCCA	This paper	N/A
RPI_04 CAAGCAGAAGACGGCATACGAGATGGAATCTCGTG ACTGGAGTTCCTTGGCACCCGAGAATTCCA	This paper	N/A
RPI_05 CAAGCAGAAGACGGCATACGAGATTTCTGAATGTGA CTGGAGTTCCTTGGCACCCGAGAATTCCA	This paper	N/A
RPI_06 CAAGCAGAAGACGGCATACGAGATACGAATTCGTG ACTGGAGTTCCTTGGCACCCGAGAATTCCA	This paper	N/A
RPI_07 CAAGCAGAAGACGGCATACGAGATAGCTTCAGGTG ACTGGAGTTCCTTGGCACCCGAGAATTCCA	This paper	N/A
RPI_08 CAAGCAGAAGACGGCATACGAGATGCGCATTAGTG ACTGGAGTTCCTTGGCACCCGAGAATTCCA	This paper	N/A
RPI_09 CAAGCAGAAGACGGCATACGAGATCATAGCCGGTG ACTGGAGTTCCTTGGCACCCGAGAATTCCA	This paper	N/A
RPI_10 CAAGCAGAAGACGGCATACGAGATTTCGCGGAGTG ACTGGAGTTCCTTGGCACCCGAGAATTCCA	This paper	N/A
RPI_11 CAAGCAGAAGACGGCATACGAGATGCGCGAGAGTG ACTGGAGTTCCTTGGCACCCGAGAATTCCA	This paper	N/A
RPI_12 CAAGCAGAAGACGGCATACGAGATCTATCGCTGTG ACTGGAGTTCCTTGGCACCCGAGAATTCCA	This paper	N/A
RA3 TGGAATTCTCGGGTGCCAAGG	Illumina	N/A
RTP GCCTTGGCACCCGAGAATTCCA	Illumina	N/A
RP1 AATGATACGGCGACCACCGAGATCTACACGTTCAG AGTTCTACAGTCCGA	Illumina	N/A
SiHUWE1 GAGUUUGGAGUUUGUGAAG[dT][dT]	Heidelberger et al., 2018	N/A
sgRNA HUWE1_1 AAGGCCCTGCCCAACTCCGT	This paper	N/A
sgRNA HUWE1_2 CATGCTACTGTTGGCTATCC	This paper	N/A
Recombinant DNA
pGex-4T3	Pharmacia	N/A
pGex-4T3-MYC1–163	Baluapuri et al., 2019	N/A
pGex-4T3-MYC1–163 DMBI	This Paper	N/A
pGex-4T3-MYC1–163 DMBII	This Paper	N/A
pInducer10	Trono Laboratory	N/A
pGIPZ	Dharmacon	N/A
psPAX2	Trono Laboratory	Addgene 12260
pMD2.G	Trono Laboratory	Addgene 12259
PX459	Zhang Laboratory	Addgene 62988
Software and Algorithms
FASTQ Generation software v1.0.0	Illumina	http://illumina.com
FastQC v0.11.3	http://www.bioinformatics.babraham.ac.uk/projects/fastqc/	https://www.bioinformatics.babraham.ac.uk/projects/fastqc/
Tophat v2.1.0	Kim et al., 2013	https://ccb.jhu.edu/software/tophat/index.shtml
Bowtie v1.2	Langmead et al., 2009	http://bowtie-bio.sourceforge.net/index.shtml
Bowtie v2.3.2	Langmead and Salzberg, 2012	http://bowtie-bio.sourceforge.net/bowtie2/index.shtml
MACS v1.4.1	Zhang et al., 2008	https://github.com/taoliu/MACS
BEDtools v2.26.0	Quinlan and Hall, 2010	https://bedtools.readthedocs.io/en/latest/
SAMtools v1.3	Li et al., 2009	http://www.htslib.org/
NGSplot v2.61	Shen et al., 2014	https://github.com/shenlab-sinai/ngsplot
Integrated Genome Browser v9.0.0	Freese et al., 2016	https://bioviz.org/
GraphPad Prism v5/6.0 for Mac	GraphPad software	https://www.graphpad.com/scientific-software/prism/
Harmony High Content Imaging and Analysis Software	PerkinElmer	http://www.perkinelmer.de/product/harmony-4-8-office-hh17000001
StepOne software v2.3	StepOne	https://www.thermofisher.com/de/de/home/technical-resources/software-downloads/StepOne-and-StepOnePlus-Real-Time-PCR-System.html
BD FACSDIVA Software v6.1.2	BD	http://www.bdbiosciences.com/us/instruments/research/software/flow-cytometry-acquisition/bd-facsdiva-software/m/111112/overview
EdgeR	Robinson et al., 2010	https://bioconductor.org/packages/release/bioc/html/edgeR.html
R version 3.6.3	The R Foundation	https://www.R-project.org/
UMI-tools v1.0.0	Smith et al., 2017	https://umi-tools.readthedocs.io/en/latest/index.html
DeepTools	Ramirez et al., 2016	https://deeptools.readthedocs.io/en/develop/
Image Studio version 5.2.5	LI-COR	http://opensource.licor.com/licenses/ImageStudio/index.html
MaxQuant version 1.5.2.8	Cox and Mann, 2008	https://www.maxquant.org/