. Author manuscript; available in PMC: 2013 Dec 31.

Published in final edited form as: Cancer Lett. 2012 Feb 19;327(1-2):61–72. doi: 10.1016/j.canlet.2012.02.001

Table 4.

The major steps and protein participants in G1 phase and S phase ICL repair.

ICL REPAIR STEP		PROTEIN	BIOCHEMICAL ACTIVITY	SUBSTRATE
RECOGNITION	G1 Phase	XPC	(See Table 3, general genome NER)	Helix distorting DNA damage
	G1 Phase	MUTSβ (MSH2-MSH3)	DNA binding	DNA Mismatch/insertion-deletion
	S Phase	FANCM/FAAP24	ATPase/replication fork regression	Collapsed replication fork
		FA Core Complex (A,B,C,E,F,G, FAAP100)	DNA damage signaling	FANCM-Replication fork complex
		FANCL + FA Core Complex	Ubiquitin ligase	FANCD2-I
ICL UNHOOKING	G1 Phase	MLH1-PMS2	Incision
	G1 Phase	ERCC1/XPF (ERCC4)	Incision (catalyzed by XPF)	3′-Flap
	S Phase	ERCC1/XPF (ERCC4)	Incision (catalyzed by XPF)	3′-Flap
		MUS81/EME1	Incision	3′-Flap
		FAN1	Incision
ICL BYPASS POLYMERIZATION^*		REV1	Deoxycytosine transferase	ICL remnant-containing DNA gap
		POLζ	Translesion DNA polymerase	ICL remnant-containing DNA gap
		POLκ	Translesion DNA polymerase	ICL remnant-containing DNA gap
		POLν	Translesion DNA polymerase	ICL remnant-containing DNA gap
ICL REMNANT REMOVAL		NER	(See Table 3, general genome NER)	Three-stranded ICL remnant
ICL REMNANT REMOVAL		NEIL1	(See Table 2, glycosylase step)	Three-stranded ICL remnant

Several translesion DNA polymerases may participate in bypass synthesis. In addition, homologous recombination (HR) events and proteins (not listed) are critical in S phase resolution of ICLs and reestablishment of a functional replication fork.