Table 1.

Key reagents and resource

Reagent or ResourceSourceIdentifier
Antibodies 
Rabbit anti-Sun2 Christian Schlieker lab (Yale University) (Rose et al., 2014) N/A 
Rabbit anti-Sun2 Christopher Carroll lab (Yale University) N/A 
Rabbit anti-LBR Christopher Carroll lab (Yale University) N/A 
Rabbit anti-Sun1 Atlas antibodies Cat# HPA008346, RRID:AB_1080462 
Mouse anti-Lamin A/C Santa Cruz Biotechnology Cat# sc-376248, RRID:AB_10991536 
Rabbit anti-Lamin B1 Abcam Cat# ab16048, RRID:AB_443298 
Rabbit anti-emerin Proteintech Cat# 10351-1-AP, RRID:AB_2100056 
Rabbit anti-Lipin 1 Millipore Sigma Cat# ABS400 (discontinued) 
Rabbit anti-NRF2 Abcam Cat# ab62352, RRID:AB_944418 
Mouse anti-mNeonGreen ChromoTek Cat# 32f6-100, RRID:AB_2827566 
Mouse anti-HA Enzo Cat# ENZ-ABS120 
Rabbit anti-HA Cell Signaling Technologies Cat# 3724; RRID: AB_1549585 
Rabbit anti-Flag Sigma-Aldrich Cat# F3165, RRID:AB_259529 
Mouse anti-tubulin alpha Millipore Cat# 05-829, RRID:AB_310035 
Bacterial and virus strains 
E. coli BL21(DE3) cells New England Biolabs Cat# C2527 
Chemicals, peptides, and recombinant proteins 
Propranolol Millipore Sigma Cat# 537075 
Puromycin Thermo Fisher Cat# A1113803 
TOFA Cayman Chemicals Cat# 10005263 
1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) (chloroform) Avanti Cat# 850457C 
18:1 (Δ9-Cis) PC (DOPC) Avanti Cat# 850375C 
18:1 (Δ9-Cis) PE (DOPE) Avanti Cat# 850725C 
18:1 DG (DAG) Avanti Cat# 800811C 
1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) Avanti Cat# 850355C 
Cholesterol Sigma-Aldrich Cat# C3045 
Pierce Glutathione Agarose Thermo Fisher Scientific Cat# 16100 
Digitonin Sigma-Aldrich Cat# D5628 
Cycloheximide Cell Signaling Cat# 2112 
3-Indoleacetic acid (IAA) Sigma-Aldrich Cat# I3750 
ProLong Gold Antifade Mountant with DAPI Thermo Fisher Scientific Cat# P36935 
Experimental models: Cell lines 
U2OS Slack lab (Harvard Medical School) N/A 
U2OS CTDNEP1^EGFP This study N/A 
U2OS mNeonGreen-NLS-2xC1ab (INM-DAG biosensor) stable This study N/A 
DLD-1 OsTIR-1 stable (Holland et al., 2012) N/A 
DLD-1 OsTIR-1 stable CTDNEP1EN-mAID-HA This study N/A 
HEK293T Breslow lab (Yale University) N/A 
Oligonucleotides 
siGENOME non-targeting siRNA Pool #2 Dharmacon Cat# D-001206-14-05 
CTDNEP1 SMARTpool siRNA (Merta et al., 2021) Dharmacon Cat# M-017869-00-0005 
Lipin 1 custom single siRNA, no modifications: 5′-GAA​UGG​AAU​GCC​AGC​UGA​A-3′ (Brohée et al., 2015; Sołtysik et al., 2021)
Dharmacon 
N/A 
Silencer select siRNA against human LMNA Thermo Fisher Cat# AM16708; assay ID 144426 
BTRC&FBXW11 custom single siRNA (targeting both genes), no modifications: 5′-GUG​GAA​UUU​GUG​GAA​CAU​C-3′ (Kim et al., 2015)
Dharmacon 
N/A 
qPCR primer: Hs Sun2 forward: 5′-TGA​CGT​GCC​TGA​CGT​ATG​G-3′ Primer Bank (Wang et al., 2012) PrimerBank ID 313760642c1 
qPCR primer: Hs Sun2 reverse: 3′-AAA​TGT​GGC​GAT​GAG​TCT​CTG-5′ Primer Bank PrimerBank ID 313760642c1 
qPCR primer: Hs CTDNEP1 forward: 5′-CAT​TTA​CCT​TCT​GCG​GAG​GC-3′ (Merta et al., 2021) N/A 
qPCR primer: Hs CTDNEP1 reverse: 3′-CAC​CTG​GGC​TAG​CCG​ATT​C-5′ (Merta et al., 2021) N/A 
qPCR primer: Hs 36B4 forward: 5′-AAC​ATG​CTC​AAC​ATC​TCC​CC-3′ (Neuhaus et al., 2011) N/A 
qPCR primer: Hs 36B4 reverse: 3′-CCG​ACT​CCT​CCG​ACT​CTT​C-5′ (Neuhaus et al., 2011) N/A 
Recombinant DNA 
CTDNEP1-GFP HR template This study N/A 
pSPCas9(BB)-2A-Puro (PX459) v2.0 (Ran et al., 2013) Cat #62988; RRID: Addgene_62988 
pX459 CTDNEP1_HR7 This study N/A 
POM121-mCherry (Dultz et al., 2008) Euroscarf #P30554 
sfCherry2(1-10) (Feng et al., 2017) RRID:Addgene_82602 
sfCherry2(11)_H2B (Feng et al., 2017) RRID:Addgene_82605 
pcDNA CTDNEP1-sfCherry2(1-10) This study N/A 
Flag-sfCherry2(1-10)-NEP1R1 This study N/A 
sfCherry2(11)-EGFP-H2B This study N/A 
mNeonGreen-NLS This study N/A 
mNeonGreen-NLS-1xC1ab This study N/A 
mNeonGreen-NLS-2xC1ab (INM-DAG biosensor) This study N/A 
mNeonGreen-NLS-2xC1ab (2xWG) This study N/A 
pCMV-VSV-G (Matsudaira et al., 2017) N/A 
pCG-Gal-Pol (Matsudaira et al., 2017) N/A 
pMXs-IP-EGFP (Matsudaira et al., 2017) N/A 
pMXs-IP-mNeonGreen-NLS-2xC1ab This study N/A 
CTDNEP1-mAID-HA wild-type This study N/A 
CTDNEP1-mAID-HA D67E This study N/A 
pRK5 Flag-mLipin 1β (mouse) wild-type (Peterson et al., 2011) RRID: Addgene_32005 
pRK5 Flag-mLipin 1β (mouse) D712/D714E This study N/A 
Flag-hLipin 1βRR (human, resistant to siLipin 1) wild-type This study N/A 
Flag-hLipin 1βRR (human, resistant to siLipin 1) D714E This study N/A 
Flag-DGAT1 (mouse) wild-type (Sołtysik et al., 2021; Xu et al., 2012) N/A 
Flag-DGAT1 (mouse) H426A This study N/A 
mScaret-I-DGAT1 (mouse) wild-type This study N/A 
mScaret-I-DGAT1 (mouse) H426A This study N/A 
Venus-DGAT2 (human) wild-type (Sołtysik et al., 2021; Xu et al., 2012) N/A 
Venus-DGAT2 (human) H163A This study N/A 
GFP-Sec61β Gia Voeltz lab N/A 
GFP-CHMP7 under CMVΔ5 (Gu et al., 2017) RRID: Addgene_97006 
Sun2 (human)-mNeonGreen This study N/A 
Sun1 (human)-mNeonGreen This study N/A 
Sun1(1-219)-Sun2(213-717)-mNeonGreen This study N/A 
Sun2(1-209)-Sun1(220-716)-mNeonGreen This study N/A 
Sun1(1-138)-Sun2(126-717)-mNeonGreen This study N/A 
Sun2(1-180)-Sun1(191-716)-mNeonGreen This study N/A 
Sun2(1-150)-Sun1(156-716)-mNeonGreen This study N/A 
pGEX-6P-1 GST-AH This study N/A 
pGEX-6P-1 GST-AH (LVW/A) This study N/A 
AH-mNeonGreen This study N/A 
AH-mNeonGreen-NLS This study N/A 
AH(LVW/A)-mNeonGreen-NLS This study N/A 
Sun1(156-190) (Sun1-AH)-mNeonGreen-NLS This study N/A 
HA-AH-mNeonGreen-NLS This study N/A 
Sun2 (LVW/A)-mNeonGreen This study N/A 
Sun2 (2xSA)-mNeonGreen This study N/A 
Sun2 (2xSA- LVW/A)-mNeonGreen This study N/A 
pMK292 (mAID-mCherry2-NeoR) (Natsume et al., 2016) RRID:Addgene_72830 
CTDNEP1-mAID-HA HR template This study N/A 
Software and algorithms 
FIJI (Schindelin et al., 2012) https://imagej.net/Fiji 
GraphPad Prism 9 GraphPad Software https://www.graphpad.com/scientificsoftware/prism/ 
SnapGene GSL Biotech LLC https://www.snapgene.com/ 
ImageJ file name encrypter Astha Jaiswal, Holger Lorenz https://imagej.net/plugins/blind-analysis-tools 
ImageJ StarDist (Schmidt et al., 2018) https://imagej.net/plugins/stardist 
TMHMM (Krogh et al., 2001) https://services.healthtech.dtu.dk/service.php?TMHMM-2.0 
PEP-FOLD3 (Lamiable et al., 2016; Thévenet et al., 2012) https://bioserv.rpbs.univ-paris-diderot.fr/services/PEP-FOLD3/ 
HeliQuest (Gautier et al., 2008) https://heliquest.ipmc.cnrs.fr/ 
MemBrain (Feng et al., 2022) http://www.csbio.sjtu.edu.cn/bioinf/MemBrain/ 
AmphipaSeeK (Combet et al., 2000; Sapay et al., 2006) https://npsa-prabi.ibcp.fr/cgi-bin/npsa_automat.pl?page=/NPSA/npsa_amphipaseek.html 
Clustal Omega (Madeira et al., 2022; Sievers et al., 2011) https://www.ebi.ac.uk/Tools/msa/clustalo/ 
ConSurf (Ashkenazy et al., 2016; Ashkenazy et al., 2010) https://consurf.tau.ac.il/ 
Python version 3.8 Python Software Foundation https://www.python.org/ 
Anaconda Anaconda Inc https://www.anaconda.com/products/distribution 
Reagent or ResourceSourceIdentifier
Antibodies 
Rabbit anti-Sun2 Christian Schlieker lab (Yale University) (Rose et al., 2014) N/A 
Rabbit anti-Sun2 Christopher Carroll lab (Yale University) N/A 
Rabbit anti-LBR Christopher Carroll lab (Yale University) N/A 
Rabbit anti-Sun1 Atlas antibodies Cat# HPA008346, RRID:AB_1080462 
Mouse anti-Lamin A/C Santa Cruz Biotechnology Cat# sc-376248, RRID:AB_10991536 
Rabbit anti-Lamin B1 Abcam Cat# ab16048, RRID:AB_443298 
Rabbit anti-emerin Proteintech Cat# 10351-1-AP, RRID:AB_2100056 
Rabbit anti-Lipin 1 Millipore Sigma Cat# ABS400 (discontinued) 
Rabbit anti-NRF2 Abcam Cat# ab62352, RRID:AB_944418 
Mouse anti-mNeonGreen ChromoTek Cat# 32f6-100, RRID:AB_2827566 
Mouse anti-HA Enzo Cat# ENZ-ABS120 
Rabbit anti-HA Cell Signaling Technologies Cat# 3724; RRID: AB_1549585 
Rabbit anti-Flag Sigma-Aldrich Cat# F3165, RRID:AB_259529 
Mouse anti-tubulin alpha Millipore Cat# 05-829, RRID:AB_310035 
Bacterial and virus strains 
E. coli BL21(DE3) cells New England Biolabs Cat# C2527 
Chemicals, peptides, and recombinant proteins 
Propranolol Millipore Sigma Cat# 537075 
Puromycin Thermo Fisher Cat# A1113803 
TOFA Cayman Chemicals Cat# 10005263 
1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) (chloroform) Avanti Cat# 850457C 
18:1 (Δ9-Cis) PC (DOPC) Avanti Cat# 850375C 
18:1 (Δ9-Cis) PE (DOPE) Avanti Cat# 850725C 
18:1 DG (DAG) Avanti Cat# 800811C 
1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) Avanti Cat# 850355C 
Cholesterol Sigma-Aldrich Cat# C3045 
Pierce Glutathione Agarose Thermo Fisher Scientific Cat# 16100 
Digitonin Sigma-Aldrich Cat# D5628 
Cycloheximide Cell Signaling Cat# 2112 
3-Indoleacetic acid (IAA) Sigma-Aldrich Cat# I3750 
ProLong Gold Antifade Mountant with DAPI Thermo Fisher Scientific Cat# P36935 
Experimental models: Cell lines 
U2OS Slack lab (Harvard Medical School) N/A 
U2OS CTDNEP1^EGFP This study N/A 
U2OS mNeonGreen-NLS-2xC1ab (INM-DAG biosensor) stable This study N/A 
DLD-1 OsTIR-1 stable (Holland et al., 2012) N/A 
DLD-1 OsTIR-1 stable CTDNEP1EN-mAID-HA This study N/A 
HEK293T Breslow lab (Yale University) N/A 
Oligonucleotides 
siGENOME non-targeting siRNA Pool #2 Dharmacon Cat# D-001206-14-05 
CTDNEP1 SMARTpool siRNA (Merta et al., 2021) Dharmacon Cat# M-017869-00-0005 
Lipin 1 custom single siRNA, no modifications: 5′-GAA​UGG​AAU​GCC​AGC​UGA​A-3′ (Brohée et al., 2015; Sołtysik et al., 2021)
Dharmacon 
N/A 
Silencer select siRNA against human LMNA Thermo Fisher Cat# AM16708; assay ID 144426 
BTRC&FBXW11 custom single siRNA (targeting both genes), no modifications: 5′-GUG​GAA​UUU​GUG​GAA​CAU​C-3′ (Kim et al., 2015)
Dharmacon 
N/A 
qPCR primer: Hs Sun2 forward: 5′-TGA​CGT​GCC​TGA​CGT​ATG​G-3′ Primer Bank (Wang et al., 2012) PrimerBank ID 313760642c1 
qPCR primer: Hs Sun2 reverse: 3′-AAA​TGT​GGC​GAT​GAG​TCT​CTG-5′ Primer Bank PrimerBank ID 313760642c1 
qPCR primer: Hs CTDNEP1 forward: 5′-CAT​TTA​CCT​TCT​GCG​GAG​GC-3′ (Merta et al., 2021) N/A 
qPCR primer: Hs CTDNEP1 reverse: 3′-CAC​CTG​GGC​TAG​CCG​ATT​C-5′ (Merta et al., 2021) N/A 
qPCR primer: Hs 36B4 forward: 5′-AAC​ATG​CTC​AAC​ATC​TCC​CC-3′ (Neuhaus et al., 2011) N/A 
qPCR primer: Hs 36B4 reverse: 3′-CCG​ACT​CCT​CCG​ACT​CTT​C-5′ (Neuhaus et al., 2011) N/A 
Recombinant DNA 
CTDNEP1-GFP HR template This study N/A 
pSPCas9(BB)-2A-Puro (PX459) v2.0 (Ran et al., 2013) Cat #62988; RRID: Addgene_62988 
pX459 CTDNEP1_HR7 This study N/A 
POM121-mCherry (Dultz et al., 2008) Euroscarf #P30554 
sfCherry2(1-10) (Feng et al., 2017) RRID:Addgene_82602 
sfCherry2(11)_H2B (Feng et al., 2017) RRID:Addgene_82605 
pcDNA CTDNEP1-sfCherry2(1-10) This study N/A 
Flag-sfCherry2(1-10)-NEP1R1 This study N/A 
sfCherry2(11)-EGFP-H2B This study N/A 
mNeonGreen-NLS This study N/A 
mNeonGreen-NLS-1xC1ab This study N/A 
mNeonGreen-NLS-2xC1ab (INM-DAG biosensor) This study N/A 
mNeonGreen-NLS-2xC1ab (2xWG) This study N/A 
pCMV-VSV-G (Matsudaira et al., 2017) N/A 
pCG-Gal-Pol (Matsudaira et al., 2017) N/A 
pMXs-IP-EGFP (Matsudaira et al., 2017) N/A 
pMXs-IP-mNeonGreen-NLS-2xC1ab This study N/A 
CTDNEP1-mAID-HA wild-type This study N/A 
CTDNEP1-mAID-HA D67E This study N/A 
pRK5 Flag-mLipin 1β (mouse) wild-type (Peterson et al., 2011) RRID: Addgene_32005 
pRK5 Flag-mLipin 1β (mouse) D712/D714E This study N/A 
Flag-hLipin 1βRR (human, resistant to siLipin 1) wild-type This study N/A 
Flag-hLipin 1βRR (human, resistant to siLipin 1) D714E This study N/A 
Flag-DGAT1 (mouse) wild-type (Sołtysik et al., 2021; Xu et al., 2012) N/A 
Flag-DGAT1 (mouse) H426A This study N/A 
mScaret-I-DGAT1 (mouse) wild-type This study N/A 
mScaret-I-DGAT1 (mouse) H426A This study N/A 
Venus-DGAT2 (human) wild-type (Sołtysik et al., 2021; Xu et al., 2012) N/A 
Venus-DGAT2 (human) H163A This study N/A 
GFP-Sec61β Gia Voeltz lab N/A 
GFP-CHMP7 under CMVΔ5 (Gu et al., 2017) RRID: Addgene_97006 
Sun2 (human)-mNeonGreen This study N/A 
Sun1 (human)-mNeonGreen This study N/A 
Sun1(1-219)-Sun2(213-717)-mNeonGreen This study N/A 
Sun2(1-209)-Sun1(220-716)-mNeonGreen This study N/A 
Sun1(1-138)-Sun2(126-717)-mNeonGreen This study N/A 
Sun2(1-180)-Sun1(191-716)-mNeonGreen This study N/A 
Sun2(1-150)-Sun1(156-716)-mNeonGreen This study N/A 
pGEX-6P-1 GST-AH This study N/A 
pGEX-6P-1 GST-AH (LVW/A) This study N/A 
AH-mNeonGreen This study N/A 
AH-mNeonGreen-NLS This study N/A 
AH(LVW/A)-mNeonGreen-NLS This study N/A 
Sun1(156-190) (Sun1-AH)-mNeonGreen-NLS This study N/A 
HA-AH-mNeonGreen-NLS This study N/A 
Sun2 (LVW/A)-mNeonGreen This study N/A 
Sun2 (2xSA)-mNeonGreen This study N/A 
Sun2 (2xSA- LVW/A)-mNeonGreen This study N/A 
pMK292 (mAID-mCherry2-NeoR) (Natsume et al., 2016) RRID:Addgene_72830 
CTDNEP1-mAID-HA HR template This study N/A 
Software and algorithms 
FIJI (Schindelin et al., 2012) https://imagej.net/Fiji 
GraphPad Prism 9 GraphPad Software https://www.graphpad.com/scientificsoftware/prism/ 
SnapGene GSL Biotech LLC https://www.snapgene.com/ 
ImageJ file name encrypter Astha Jaiswal, Holger Lorenz https://imagej.net/plugins/blind-analysis-tools 
ImageJ StarDist (Schmidt et al., 2018) https://imagej.net/plugins/stardist 
TMHMM (Krogh et al., 2001) https://services.healthtech.dtu.dk/service.php?TMHMM-2.0 
PEP-FOLD3 (Lamiable et al., 2016; Thévenet et al., 2012) https://bioserv.rpbs.univ-paris-diderot.fr/services/PEP-FOLD3/ 
HeliQuest (Gautier et al., 2008) https://heliquest.ipmc.cnrs.fr/ 
MemBrain (Feng et al., 2022) http://www.csbio.sjtu.edu.cn/bioinf/MemBrain/ 
AmphipaSeeK (Combet et al., 2000; Sapay et al., 2006) https://npsa-prabi.ibcp.fr/cgi-bin/npsa_automat.pl?page=/NPSA/npsa_amphipaseek.html 
Clustal Omega (Madeira et al., 2022; Sievers et al., 2011) https://www.ebi.ac.uk/Tools/msa/clustalo/ 
ConSurf (Ashkenazy et al., 2016; Ashkenazy et al., 2010) https://consurf.tau.ac.il/ 
Python version 3.8 Python Software Foundation https://www.python.org/ 
Anaconda Anaconda Inc https://www.anaconda.com/products/distribution 

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