TABLE 1.

DPC-modifying PTM writers and readers.

PTM	Enzyme	Functions/pathways	Investigated DPC substrates
PTM Writers
Ubiquitylation	TRAIP	Replisome component, ubiquitylates target proteins in front of replication forks	M.HpaII-DPC (Larsen et al., 2019)
	RFWD3	Binds to the ssDNA associated protein RPA, ubiquitylates target proteins on ssDNA	M.HpaII-DPC (Gallina et al., 2021)
			Fpg-DPC (Gallina et al., 2021)
			HMCES-DPC (Gallina et al., 2021)
	TRIP12	PAR-targeted ubiquitin ligase, ubiquitylates PARP1	PARP1-trapping (Gatti et al., 2020)
	RNF4	SUMO-targeted ubiquitylation pathway	M.HpaII-DPC (Liu et al., 2021)
			DNMT1-DPC (Liu et al., 2021)
			TOP1-DPC (Sun et al., 2020)
			TOP2-DPC (Sun et al., 2020)
			PARP1-trapping (Krastev et al., 2022)
	TRIM41	Ubiquitylates TOP3B-DPC	TOP3B-DPC (Saha et al., 2020)
	Slx5-Slx8	SUMO-targeted ubiquitylation pathway	TOP1-DPC (Heideker et al., 2011; Steinacher et al., 2013; Nie et al., 2017)
			TOP2-DPC (Wei et al., 2017)
	CUL3	Scaffold protein in Cullin-RING E3 ligase complex	TOP1-DPC (Zhang et al., 2004)
	CUL4B	Scaffold protein in Cullin-RING E3 ligase complex	TOP1-DPC (Kerzendorfer et al., 2010)
	BRCA1	Contributes to transcription-dependent TOP1-DPC degradation	TOP1-DPC (Sordet et al., 2008)
	BMI1-RING1A	Ubiquitylates TOP2-DPC	TOP2-DPC (Alchanati et al., 2009)
	SCFβ-TrCP	SKP1-Cullin 1-F box protein	TOP2β-DPC (Shu et al., 2020)
SUMOylation	ZATT/ZNF451	SUMOylates TOP2-DPC and stimulates TDP2-mediated hydrolysis	TOP2-DPC (Schellenberg et al., 2017)
	PIAS4	SUMO-targeted ubiquitylation pathway	M.HpaII-DPC (Liu et al., 2021)
			DNMT1-DPC (Liu et al., 2021)
			TOP1-DPC (Sun et al., 2020)
			TOP2-DPC (Sun et al., 2020)
			PARP1-trapping (Liu et al., 2021; Krastev et al., 2022)
	Pli1	SUMO-targeted ubiquitylation pathway	TOP1-DPC (Steinacher et al., 2013)
	Nse2	SUMO-targeted ubiquitylation pathway	TOP1-DPC (Heideker et al., 2011)
PARylation	PARP1	PARP1 auto-PARylation limits PARP1 trapping, recruits PTUbLs or deubiquitylation enzymes	PARP1-trapping (Prasad et al., 2014; Steffen et al., 2016; Gatti et al., 2020; Kruger et al., 2020)
			TOP1-DPC (Sun et al., 2021)
PTM Readers/Effectors
Ubiquitylation	Proteasome	DPC proteolysis	M.HpaII-DPC (Larsen et al., 2019)
			DNMT1-DPC (Liu et al., 2021)
			TOP1-DPC (Desai et al., 1997; Mao et al., 2000b; Desai et al., 2003; Zhang et al., 2004; Lin et al., 2008; Sordet et al., 2008; Kerzendorfer et al., 2010; Heideker et al., 2011; Steinacher et al., 2013; Nie et al., 2017; Sun et al., 2020; Sun et al., 2021)
			TOP2-DPC (Mao et al., 2001; Wei et al., 2017; Sun et al., 2020)
			TOP3B-DPC (Saha et al., 2020)
			Polβ-DPC (Quinones et al., 2015; Quinones et al., 2020)
			PARP1-trapping (Prasad et al., 2019; Gatti et al., 2020)
			Flp-DPC (Ma et al., 2019)
			HMCES-DPC (Mohni et al., 2019)
	SPRTN a	DPC proteolysis	M.HpaII-DPC (Larsen et al., 2019)
			TOP1-DPC (Vaz et al., 2016; Maskey et al., 2017)
			TOP2-DPC (Lopez-Mosqueda et al., 2016; Vaz et al., 2016)
			HMCES-DPC (Semlow et al., 2022)
			Formaldehyde-induced DPCs (Lopez-Mosqueda et al., 2016; Stingele et al., 2016; Borgermann et al., 2019; Ruggiano et al., 2021)
	p97	Unfoldase activity for trapped protein	PARP1-trapping (Krastev et al., 2022)
			Eos-DPC (Kroning et al., 2022)
	Ddi1/DDI2 a	DPC proteolysis	TOP1-DPC (Serbyn et al., 2020)
			Flp-DPC (Serbyn et al., 2020)
SUMOylation	RNF4	SUMO-targeted ubiquitylation	M.HpaII-DPC (Liu et al., 2021)
			DNMT1-DPC (Liu et al., 2021)
			TOP1-DPC (Sun et al., 2020)
			TOP2-DPC (Sun et al., 2020)
			PARP1-trapping (Krastev et al., 2022)
	Slx5-Slx8	SUMO-targeted ubiquitylation	Flp-DPC (Ma et al., 2019)
			Top1-DPC (Heideker et al., 2011; Steinacher et al., 2013; Nie et al., 2017)
			Top2-DPC (Wei et al., 2017)
	TDP2	5′-Y hydrolysis	TOP2-DPC (Schellenberg et al., 2017)
	TEX264	Recruit DPC repair factors	TOP1-DPC (Fielden et al., 2020)
	Wss1	DPC proteolysis	Top1-DPC (Stingele et al., 2014)
			Formaldehyde-induced DPC (Stingele et al., 2014)
	ACRC a	DPC proteolysis	TOP2-DPC (Bhargava et al., 2020; Dokshin et al., 2020)
			Formaldehyde-induced DPC (Borgermann et al., 2019)
	SPRTN a	DPC proteolysis	TOP1-DPC (Ruggiano et al., 2021)
			Formaldehyde-induced DPC (Ruggiano et al., 2021)
PARylation	TRIP12	PARylation-targeted ubiquitylation	PARP1-trapping (Gatti et al., 2020)
	USP7 a	Deubiquitylating enzyme	TOP1-DPC (Sun et al., 2021)

^aPutative DPC-PTM readers.