KEY RESOURCES TABLE

REAGENT or RESOURCE	SOURCE	IDENTIFIER
Antibodies
Rabbit monoclonal (Y69) anti-c-myc	Abcam	Cat#ab32072
Mouse monoclonal anti-hsp90	BD Transduction Laboratories	Cat#610419
Rabbit monoclonal anti-hsp90	Cell Signaling Technologies	Cat#4877S
Rabbit polyclonal anti-p53	Leica	Cat#P53-CM5P-L
Rabbit Anti-Mouse IgG (H&L)	Abcam	Cat#ab46540
Rabbit polyclonal anti-pHH3 Serine 10	Cell Signaling Technologies	Cat#9701S
Goat Anti-Mouse IgG (H + L)-HRP Conjugate	Bio-Rad	Cat#1706516
Peroxidase AffiniPure Donkey Anti-Rabbit IgG (H+L)	Jackson ImmunoResearch	Cat#711-035-152
Bacterial and Virus Strains
Stable Competent E.coli (High Efficiency)	New England Biolabs	Cat#C3040H
5-alpha Competent E.coli (High Efficiency)	New England Biolabs	Cat#C2987U
Chemicals, Peptides, and Recombinant Proteins
4-hydroxy tamoxifen	Cayman Chemical Company	Cat#17308-10
Doxorubicin hydrochloride	Sigma-Aldrich	Cat#D1515-10MG
Etoposide	Millipore Sigma	Cat#E1383-25MG
Cycloheximide	Sigma-Aldrich	Cat#C4859-1ML
Hexadimethrine bromide (polybrene)	Millipore Sigma	Cat#107689-10G
Puromycin dihydrochloride	Sigma-Aldrich	Cat#58-58-2
Hygromycin B	Roche	Cat#10843555001
DMEM, high glucose, pyruvate	Gibco	Cat#11995065
Fetal Bovine Serum	Sigma-Aldrich	Cat#F0926-500ML
L-Glutamine	Gibco	Cat#25030-081
Pen-strep	Gibco	Cat#15140-122
NEAA	Gibco	Cat#11140-050
2-mercaptoethanol	Gibco	Cat#21985023
SYBR Fast Master Mix	Kapa Biosystems	Cat#kk4602
Nitrocellulose membranes	Bio-Rad	Cat#1620112
ECL Prime Western Blotting detection reagent	GE Healthcare	Cat#RPN2232
Methanol-free formaldehyde	Thermo Scientific	Cat#28908
cOmplete, Mini Protease Inhibitor Cocktail	Roche	Cat#4693124001
PureProteome Protein G Magnetic Beads	Millipore Sigma	Cat#LSKMAGG02
Salmon Sperm DNA	Invitrogen	Cat#15632011
Mouse Cot-1 DNA	Invitrogen	Cat#18440016
Proteinase K	Roche	Cat#03115879001
Formamide	Millipore Sigma	Cat#F9037-100ML
Stellaris® RNA FISH Hybridization Buffer	LGC Biosciences	Cat#SMF-HB1-10
Stellaris® RNA FISH Wash Buffer A	LGC Biosciences	Cat#SMF-WA1-60
Stellaris® RNA FISH Wash Buffer B	LGC Biosciences	Cat#SMF-WB1-20
VECTASHIELD® Antifade Mounting Medium with DAPI	Vector Laboratories	Cat#H-1200
Alexa Fluor® 488-5-UTP	Invitrogen	Cat#C11397
Alexa Fluor® 594-5-UTP	Invitrogen	Cat#C11400
TRIzol Reagent	Invitrogen	Cat#15-596-018
TRIzol-LS Reagent	Invitrogen	Cat#10296028
RNasin Plus RNase inhibitor	Promega	Cat#N2615
CutSmart® Buffer	New England Biolabs	Cat#B7204S
BamHI-HF®	New England Biolabs	Cat#R3136L
T4 DNA Ligase	New England Biolabs	Cat#M0202L
Adenosine 5'-Triphosphate (ATP)	New England Biolabs	Cat#P0756L
4-thiouridine (s4U)	Alfa Aesar	Cat#AAJ60679MC
TURBO DNase	Invitrogen	Cat#AM2238
Agencourt RNAclean XP beads	Beckman Coulter	Cat#A63987
MTSEA biotin-XX	Biotium	Cat#900661
Critical Commercial Assays
Mouse/Hepatocyte Nucleofector Kit	Lonza	Cat#VPL1004
RNeasy Mini Kit	Qiagen	Cat#Q74106
High Capacity cDNA Reverse Transcription Kit	Applied Biosystems	Cat#Q74106
Zero Blunt TOPO PCR Cloning Kit	Invitrogen	Cat#450245
Nucleobond Xtra BAC kit	Takara Bio USA	Cat#740436.10
Nick Translation System	Invitrogen	Cat#18160-010
TruSeq Stranded mRNA Library Prep	Illumina	Cat#20020594
Clontech SMARTer Stranded Total RNA-Seq kit Pico Input Mammalian	Takara Bio USA	Cat#634411
Vectastain Elite ABC-HRP Kit (Peroxidase, rabbit IgG)	Vector Laboratories	Cat#PK-6101
DAB Peroxidase (HRP) Substrate Kit	Vector Laboratories	Cat#SK-4100
Deposited Data
Raw and analyzed data of mouse cell line	This study	GEO: GSE126940
Experimental Models: Cell Lines
Mouse: Primary WT embryonic fibroblasts (MEFs)	This paper	N/A
Mouse: K-rasG12D/+; p53LSL/LSL; Rosa-CreERT2 (KPR8) cell line	Feldser et al., 2010	N/A
Mouse: p53LSL/LSL; Rosa-CreERT2 (p53-restorable MEFs)	Ventura et al., 2007	N/A
Mouse: 3TZ (3T3 derivative) cell line	T. Jacks, MIT	N/A
Human: fetal lung fibroblasts (TIG-1)	NIA Aging Cell Culture Repository	Cat#NG06173
Experimental Models: Organisms/Strains
Mouse: Wild-type (WT) C57BL/6J	Jackson Laboratories	Cat#000664
Mouse: K-rasLSL-G12D/+ (K)	Jackson et al., 2001; Jackson Laboratories	Cat#008179
Mouse: p53FL/FL (P)	Jackson et al., 2005; Jackson Laboratories	Cat#008462
Mouse: Rosa26-Cas9LSL/LSL (C)	Platt et al., 2014; Jackson Laboratories	Cat#026556
Oligonucleotides
qRT-PCR primers, see Table S1	This paper	N/A
PCR primers, see Table S1	This paper	N/A
smRNA FISH probes, see Table S1	This paper	see Table S1
3C qPCR primers, see Table S1	This paper	N/A
ChIP qPCR primers, see Table S1	This paper	N/A
ASO sequences, see Table S1	This paper	see Table S1
sgRNA sequences, see Table S1	This paper; Xue et al., 2014	N/A
dRNA sequences, see Table S1	This paper	N/A
Recombinant DNA
pCMV-dR8.2 dvpr	Stewart et al., 2003	Addgene #8455
pCMV-VSV-G	Stewart et al., 2003	Addgene #8454
pWZL Hygro	S. Lowe, unpublished	Addgene #18750
BRD001	Broad Institute	N/A
BRD004	Broad Institute	N/A
UGPC	This paper	N/A
lenti-SAM-hygro	This paper	N/A
Myc BAC	BACPAC Resources Center	Cat#RP23-55F11
Chr 6 BAC	BACPAC Resources Center	Cat#RP24-301E22
Software and Algorithms
GraphPad Prism, version 8.2.1 for MacOS	N/A	www.graphpad.com
Biorender	N/A	www.biorender.com
Tophat (v2.0.14)	Trapnell et al., 2009	http://ccb.jhu.edu/software/tophat/index.shtml
stringtie (v1.2.4)	Pertea et al., 2015	https://ccb.jhu.edu/software/stringtie/
HTSeq (v0.6.1)	Anders et al., 2015	https://htseq.readthedocs.io/en/release_0.11.1/
EdgeR (v3.22.3)	Robinson et al., 2010	https://bioconductor.org/packages/release/bioc/html/edgeR.html
FastUniq	Xu et al., 2012	http://sourceforge.net/projects/fastuniq/
Cutadapt (v1.16)	Martin, 2011	https://cutadapt.readthedocs.io/en/stable/
HISAT2 (v2.1.0)	Kim et al., 2015	https://ccb.jhu.edu/software/hisat2/index.shtml
SAMtools (v1.5)	Li et al., 2009	http://samtools.sourceforge.net
STAR (v2.5.3a)	Dobin et al., 2013	https://github.com/alexdobin/STAR
DEseq2	Love et al., 2014	https://bioconductor.org/packages/release/bioc/html/DESeq2.html