Table 1.

Functions and regulation of CtIP orthologs

CtIP ortholog	Organism	Protein	Function	Regulation
Sae2	S. cerevisiae	235 a.a.	DSB resection and HR in meiotic and mitotic cells [28,57–59,68,69,94–98] Acts in the same epistasis pathway as MRX in DSB resection [58,97] Recombinant protein has intrinsic endonuclease activity [56] Cooperates with MRX in removing hairpin structure [56,96,98]	S267 phosphorylation by CDK1 is required for DSB resection [28] Phosphorylation by Tel1/Mec1 is required for meiosis and cell survival after DNA damage [99,100]
Ctp1	S. pombe	294 a.a.	DSB resection and HR in meiotic and mitotic cells Acts in the same epistasis pathway as MRN in DSB resection [23,24]	Ctp1 expression is regulated by MBF [23] Ctp1 phosphorylation at CK2 SXT sites is required for Nbs1 binding [48,49]
COM1	C. elegans	525 a.a.	DSB processing in meiosis [26]	Not determined
AtGR1	A. thaliana	588 a.a.	DSB processing in meiosis [27]	Not determined
CtIP	X. laevis	856 a.a.	DSB resection in Xenopus egg extracts [18]	CtIP associated with damaged chromatin is highly modified [18] CtIP damage recruitment is regulated by MRN and ATM [18]
CtIP	Chicken	912 a.a.	HR in S and G2 phases and MMEJ in G1 phase [22,77]	CtIP S332-phosphorylation is not required for DSB resection and HR [77]
CtIP	Mouse	893 a.a.	Required for embryonic development; haploinsufficient [25] Promotes G1/S transition by activating E2F/Rb-regulated promoters [5] Transcriptional corepressor together with BRCA1 and ZBRK1 [101]	Not determined
CtIP	Human	897 a.a.	DSB resection, ATR activation and HR [9–11,16–18,73] Transcription corepressor together with CtBP, RBP-Jκ/SHARP, Ikaros and LOM4 [102,103]	Phosphorylation at S664 and S745 by ATM regulates transcription of cell cycle inhibitor genes [12] Phosphorylation at S327 and T847 by CDK, and ubiquitination by BRCA1 are required for DSB resection [73,76] CtIP protein levels are cell cycle-regulated [9,82] SIAH promotes CtIP degradation through the ubiquitin-proteosome pathway [81]