DDK (Cdc7/Hsk plus Dbf4/Dfp1)


Protein kinase required for initiation of DNA replication, probably via phosphorylation of Mcm2-7.






Molecular weight

58 kDa (Sc)

Biochemical properties


Protein kinase, requires Dbf4 for function (1) (2) Activity stimulated in vitro by polyamines and histones (3)



• nrs ( needed for localization distinct from nls) (4)



• Mcm2-7 proteins (in vitro) (5) in vivo (6) for MCM4 aids its interaction cdc45 (7)

•Mcm5/Cdc46 (bob1) mutation can suppress requirement for DDK (8)

•Dbf4 (9)

•Orc (2) (10)

•Cdc45 in vitro (11)

•Polymerase alpha in vitro (12)



•Cds1 , Rqh1, Rad21 (13)

•Swi6 (hp1) (14)

• role in sld3 origin binding (15)



•Mcm3/7 in interphase but not mitotic extracts. (16)

•Caf1 (17)

• SCC2/4 (18)



•mcm2 (19)

• claspin (20) substrate (21)

• importin beta (22)


• Autophosphorylation in vitro (23)

• Phosphorylated by cds1 in response to HU (13)

• Phosphorylated ATR in checkpoint function? (24)




Cellular location and expression


•Seen on chromatin all of the cell cycle (23)



Other comments


• odd strain dependency (25)

• needs orc for recruitment to origins (nb in higher eukaryotes needs mcm but not orc) (26)

• suggested role in silencing (27)

• suggested role in meiosis (28) (29) (30)   (31-33)

• required for the full activation of rad53 (34)

• role in rDNA segregation (35)


• Role in initiating meiotic recombination (36)

• suggested rate limiting factor for origin firing (37)



• Some debate about whether needs to act before cdc2 (38) Vs (39)

• DNA damage checkpoint works via Cdc7 (24)



• Often overexpressed in tumour cell lines (40)

• Reported splice variants in mouse (41)

• Mouse knockouts (42)

• Checkpoint role in response to uvc (43)

• Suggested role in damage response (44) in es cells (21)

• Depletion gives abortive s phase arrest (non transformed cells) and apoptosis (transformed cells) (45)

Revised by


Last edited

13 July 09






SpDfp1, SpHim1, SpRad35

Dm Chiffon (46)


An Nimo (47)


Molecular weight

81 kDa (Sc)

Biochemical properties


Regulatory subunit of Cdc7 kinase  




•APC destruction boxes (48) (49) (50)



•Zn finger; (51)



•NLS, PEST sequences (52)

•2 PEST sequences, BRCT domains (53) 1 involved in response to DNA damage (54)


•Cdc7 SC (23) Xl? (52) Sp (55)



•Mcm2 (10)

•ORC, Rad53 (56) (57) (58) (9)

•Cdc5 (59)



Swi 1 (60)

Cdc23 (Mcm10) (61)



•Mcm2 (62)




•Phosphorylated in S not G2 (23)

•Phosphorylated in nocodazole block (50)

•Phosphorylated by rad53 (9)



•3 phospho-forms slowest max just before s, disappears at end s . Intermediate peaks g2. •Cds 1 needed for hyperphosphorylation (63)



Cellular location and expression


• Level of Dbf4 varies in cell cycle (Cdc7 level is constant). Low in G1, increases in S phase. •Proteolysis is APC dependent (48) (49) (50)



• protein levels up in late s /g2 (64)

Other comments


•apc substrate (23)



Spo4/6 Nakamura et al mcb 2002 22 309.


 •2nd homologue– Drf1 (65) suggest this is the more important for replication while dbf4 involved in meiosis. (66)



• needed for binding of DDK to ORC (67)



•Related protein that also interacts with cdc7 (68)

•often overexpressed in tumour cell lines (40)

• ( also Xl) direct positive effect on overcoming DNA damage checkpoint (69)

Revised by


Last edited

13 July 09



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