Assembled onto chromatin at ORC  to form ‘pre-replicative complex’.  On replication initiation, Mcm2-7 moves away from ORC with replication fork. Probably provides helicase activity at fork, possibly in conjunction with other proteins such as GINS and Cdc45. Displaced from chromatin during S phase, probably on replication termination. (1) (2) (3) (4) (5)

Hexameric complex composed of Mcm2, Mcm3, Mcm4, Mcm5, Mcm6 & Mcm7. Note not related to Mcm1 or Mcm10.



RLF-M (Xl)

Molecular weight

Mw 2-  114 (112 phosphorylated), 3 - 100, 4- 98, 5- 92, 6- 102, 7- 90 (6)

Biochemical properties

•3’>5’ helicase activity in vitro (Mcm467) (7) (8) (9) (10) Mcm2,3,5 inhibit helicase activity

•DNA binding – ss ATP dependent (10)

ATPase (11) (12)



• analysis of properties subcomplexes (13)

• properties of mcm4/6/7 vs mcm2-7. suggest phosphorylations serve as switch between open (loading) and closed (helicase) complex. (14)

• comparison 4 7 helicase and  4 6 7 helicase activities (15)



•May function as helicase in complex with GINS and Cdc45 (16)



•Human preferential binding to T rich ssDNA

(17) but can overlap ds (18)



•Methanobacterium thermoautotrophicum -ATPase stimulated by ds but not ss DNA (19)

•Thermoplasma acidophilum helicase stimulated by cdc6 (20)

•Thermos aquaticus mcms can’t pass stalled transcription complexes (21) .

•analysis Sulfolobus solfataricus mcm - DNA binding (22) ATPase/helicase (23)


AAA+ ATPase (24)



• domain mapping (25) (26)


Mcm2-7 subunit interactions

•Subcomplexes – 4/6/7, 3/5, 2

•Hexamer/Dodecamer in methanobacterium thermoautotrophicum (19) (27) (28)

- reported as 7 membered ring (29)

Sc- Genetic - (30) (31)   Direct - (11) (12) (32)

Sp (33) (10)

Xl- (34) (6) (35) (36)

Mammals- (37) (38) (39) (40) (41) (42)

(On chromatin) (43) (44)

Dm- (45)

Archae (46)


Interactions with other proteins



•Cdc7-Dbf4  (47) (48)

•Cdt1 (49)

•Cdc6 (50)

•GINS (51)

Csm1 (spo86) (52)

Tof1/Csm3/Mrc1 (53)

•Hbo1 (54)

• cdc45 (55)



•cdc23 (mcm10) (56) genetic

•orc 1 2  5 6   (56) genetic

•rum 1 (57) – genetic

• cds1 (58)

•rhp1/rad22 (in hu) (58)



GINS (16)



Cdt1  (59)

•tfIIb,e,f,h, and tbp (60)

•Rb (61)

•Cdc45 (62)

• elys/mel (63)



Cdt1 (64) (65) (66)

•RNA polII  - (67) (68)

•Plk (69) (70)

• histones (4/6/7 complex) (71)

•suc beads - (72)

• SMC1 (73)

• FACT (74)

Rad51/Rad52 (75)

AKAP95 (76)

RPA (40) (77)


• MCM binding protein (with MCM3-7) (78)

• int6 ( MCM7 role in removal from chromatin?)


• cleavage products of Importin alpha during apoptosis (80)



• ETG1 ( E2F target gene 1) (81)


•Gins (82)



• flu virus RNA dependent RNA polymerase (83)




• in vitro 2 4 6 phosphorylated by  cdc7. (55) . Role for MCM4 phosphorylation in MCM transport (84)



• cdc7 phosphorylation sites (85)



•em studies on structure (41)


•ring structure ssDNA through the middle and the complementary strand around the outside to keep them apart. (86)

Thermoplasma acidophilum . hexamers in solution (20)

• Crystal structure of sulfolobus solfaticus MCM n terminal domain. (87)

Cryo-electron microscopy (88)

• central channel is beta hairpin domains (89)

• nearly full length Methanothermobacter thermautotrophicus (90)

Cellular location and expression


•Nuclear localization changes during cell cycle (nuclear in late M/G1 (91) (92)



•Nuclear throughout cell cycle eg (93)

•subunits appear to bind to chromatin simultaneously (94) .

•Nuclear  localisation depends on Crm1, subunits need to interact for import (95)



• some co-dependence of subunit levels (96)


•Mcm proteins only bound to chromatin late M-S phase. Some suggestion that don’t all load onto chromatin at the same time (97)



• load in telophase and early G1 (98)

• 2 populations 1 bound tightly to chromatin and one not (99)



Other comments

• Big excess compared to origins (eg yeast (100) , Xl (101) )

• xenopus extracts and Drosophila cells can reduce under normal conditions without visible effect replication (102) , (96) . In xenopus suggested role for excess in recovery from replicative stress (103) also for human (104)

• Models for helicase :

– pumping at a distance (105) .

 - modified wedge model (106)

 - Ploughshare model (107)

•Possible transcriptional role eg SC (108) mammals (109)

•Often overexpressed in transformed cells eg




• may be regulated by MRC1 (111)



• hela cells – only mcm2 and 3 can be reduced without affecting proliferation. long term these stop G2 via replication checkpoint and get activation chk1 2 and increased ss and ds DNA damage. origin firing normal but can’t be increased when add chk1 inhibitor as get for wild type cells. Increased sensitivity aphidicolin and HU. (112)



•some have 4 mcms some 1mcm, most similar to mcm4? (113)

• genome wide mapping of MCM binding sites (114)

• Methanothermobacter thermautotrophicus - the loop connecting the n and the c termini is involved in communication between the termini.


• thermoplasma acidophilum mcm and cdc6 - stimulates mcm helicase (116)

Revised by


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Molecular weight


Biochemical properties

• activities of mcm2 fragments (117)



• ATPase

• Nls SC (95) human (118)

• Zn finger (xenopus) (6)

• N-terminus alternating repeats of basic and acidic (6)


Protein interactions


• Hat1 (119) (mass screen)

• Cdc7 (62)

• Cdc6 (64)

• Hbo1 (54)



•PolII  (68)



Phosphorylation (CDK, Cdc7, ATR, ATM)





Phosphorylation sites for CDK, Cdc7, ATR related , ATM related (121) (55)

•Phosphorylated by ATR/ATM (122)

•Phosphorylation increases g1 to M (123)



•Phosphorylation by ATM/ATR (124) in response to genotoxic stress

•Phosphorylated after mitotic exit in cdk independent manner (72)



• G2/M hyperphosphorylation. Good substrate cdc2/cyclinb in vitro (125)

• Cdc7 phosphorylation g1/s. Increases ATPase of MCM2-7 complex (120) – may depend on prior phosphorylation by others (126)




Cellular location and expression


Other comments


• cleaved in senescence (85) (127)

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Hs P1

Molecular weight


Biochemical properties




•nls (human) (118)

•nes (human) (118)

• Zn finger required for activity (128) although suggested not needed in xenopus (6)

• n terminus alternating repeats of basic and acidic amino acids (6)

•human MCM3 has 4 cdk sites,  most phosphorylated in mitosis. (129)




• Map80/ganp (130) (131)

• Histone H3 (132)

MCM3AP (133)





•Phosphorylation increases g1 to M (123)

•Ub (rescue by uba1 mutant (134)



•Phosphorylation (135)



•Phosphorylation (72)

•ATR/ATM (substrate) (122) identification sites of phosphorylation (136)

• Acetylation (133) mcm3ap splice variant ganp 




Cellular location and expression


Other comments



•Protein turnover high although actual level stays the same (137)

• Cleaved by caspase 3 in apoptosis (138)


Revised by


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SpCdc21; Dm dpa

Molecular weight


Biochemical properties



• ATPase

• Zn finger   (6)

•N terminus alternating repeats of basic and acidic (6)

• pombe c terminal domain mcm4 involved in tolerating low levels dNTPs (139)



•Spt16/Pob3 (51)

•Mcm10 (140) (51)

• cdc7 (141)



•Rb (142)


Phosphorylation (CDK, ATR)




• mapping cdk sites (55) , possible role in transport (84)

• N terminus has 5 conserved cdk sites close to cdc7 sites. Not phosphorylated if cdc7 acts first (144)



• Phosphorylation twice s then up again in M (cdk) (145)

•Phosphorylated has lower affinity for chromatin




• cdk2 dependent in interphase and cdk1 dependent g2/m sites mapped (147)

•hyperphosphorylated uv /hu ATR cdk involved in HU (143) (148)

•As xenopus (125)

•2 step (72)

• phosphorylated during EB virus replication (149)




Cellular location and expression


Other comments


• have isolated point mutations where homozygous prone to tumours but males not (150)


Revised by


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ScCdc46; SpNda4

Molecular weight


Biochemical properties




•n terminus alternating repeats of basic and acidic (6)



•Cdc45 (57) – genetic

•ddk ( genetic- bob mutant), proposed mechanisms for bypass (151)



• Stat 1 (152) (153) (154)

• cyclin E (role in centrisome duplication) (155)





Cellular location and expression


Other comments


• null mutant can endoreplicate (156) .

• suggested role in chromatid cohesion (156)



• needed for post embryonic development (157)


Revised by


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Molecular weight


Biochemical properties




•Zn finger (6)

•n terminus alternating repeats of basic and acidic (6)




•Rpn and vma1 (119) (mass screen)

•Smc1 (73)



•Phosphorylation (72)



Cellular location and expression


• genome wide mcm6 binding (158)


Other comments


Revised by


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Molecular weight


Biochemical properties




•Zn finger (6)

•n terminus alternating repeats of basic and acidic (6)




•Mcm10 (140) (51)



• rad4,chk1 and cds1 synthetically lethal (159)



•Rb N terminus - (160)

• mat (161)

•Rad17 (162)

•P27kip (77)

•ATRIP (122)

•E6 (163)

•Smc1 (73)

•Plk1 (69)

• BER complex (164)



Ubiquitylation (E3-ubiquitin ligase/E6-AP)

(165) , also via int6 (79)



Cellular location and expression


Other comments



•links to tumour formation (166) (167) (168) (169) (170) (171) (172) (173)

• Expression controlled by e2f1-4 (174)

• suggested to be involved in feedback on replication (160)

Revised by


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