Table 1. E3 ligases that regulate replication fork stability.

E3 ligase	Substrate	Function	REF.
OBI1	ORC	Promotes origin firing and recruitment of DNA replication factors	[16]
SCF-Skp2 DDB1-Cul4	CDT1	Maintains low levels of CDT1 in S and G2 phase	[17]
SPOP	Geminin	Blocks the binding of CDT1 to MCM and prevents the overfiring of replication origins	[18]
SCFDia2	MCM7	Recruits CDC48 to disassemble CMG helicase, mediating termination in budding yeast	[19,20]
CUL2LRR1	MCM7	Recruits CDC48 to disassemble CMG helicase, mediating termination in metazoans	[21,22]
SCFPof3	Pol ε/δ MCM-2,-4,-6	Delays replication fork progression via the ubiquitin-proteasome system in Swi1-deficient cells	[23]
PRP19	RPA	Promotes ATR-ATRIP activation	[12]
RFWD3	RPA	Activates ATR-ATRIP and promotes PCNA ubiquitination	[24,25]
HectH9	TopBP1	Reduces TopBP1 recruitment to chromatin and attenuates ATR-dependent signaling	[26]
RAD18	PCNA	Promotes monoubiquitination of PCNA, facilitating binding to TLS polymerase, and helps to bypass problematic lesions	[27]
CRL4Cdt2	PCNA	Facilitates the TLS pathway in undamaged cells	[28].
Rad5 HLTF/SHPRH	PCNA	Promotes the TS pathway and recruits the DNA translocase ZRANB3 to stalled replication forks	[13–15]
SCFFBH1	RAD51	Prevents reassociation of RAD51 with DNA	[29]
RNF168	H2A	Prevents MRE11-dependent fork degradation	[30]
Bre1	H2B	Facilitates fork stalling and recovery during replication stress	[31,32]
MDM2	PARP1	Increases the activity of RECQ1 and PRIMPOL, promoting restart and repriming of DNA synthesis	[33]
SIAH2	CtIP	Promotes the loading of SIAH2 at stalled replication forks, facilitating efficient restart	[34]
TRAIP	DPCs	Promotes degradation of DPCs via the ubiquitin-proteasome pathway	[35]
TRAIP	CMG	Promotes CDC48/p97-dependent disassembly of CMG at ICLs and NEIL3 pathway	[36,37]
FANCL PHF9	FANCD2/FANCI	Promotes ICL repair via nuclease-dependent DNA incision carried out by XPF (FANCQ)-ERCC1 and SLX4 (FANCP) and diminishes R-loop accumulation	[38,39]

Abbreviations: DPC, DNA–protein cross-link; ICL, DNA interstrand cross-link; TLS, translesion synthesis; TS, template-switching.