ライフサイエンスコーパス: MCM5

1 at regulate DNA replication, namely Cdc6 and Mcm5.

2 two pairs of gate-forming subunits, MCM2 and MCM5.

3 dc7 displayed association with both Mcm4 and Mcm5.

4 ified a strong interaction between Stat1 and MCM5.

5 of the promoters of MCM7 as well as CDC6 and MCM5.

6 teins is due to the association of MCM3 with MCM5.

7 ay be important for an interaction domain in MCM5.

8 ent of at least two additional active sites (Mcm5/3 and 6/2) in modulating the activity of the putati

9 ma-treated cells demonstrate that there is a MCM5/3 subcomplex coeluting with Stat1.

10 sults strongly suggest that Stat1 recruits a MCM5/3 subcomplex through direct interaction with MCM5 i

11 f the interacting proteins was identified as MCM5, a member of the mini-chromosome maintenance (MCM)

12 iotically induced DSBs, flies homozygous for mcm5(A7) are fully proficient in somatic DNA repair.

13 mbination observed in females homozygous for mcm5(A7) is not due to a failure to create or repair mei

14 a viable and fertile allele of mcm5 (denoted mcm5(A7)) that specifically impairs the meiotic recombin

15 strengthens the interaction between Mcm3 and Mcm5 and allows cells to enter S phase independent of Cd

16 Sfrs5 and Sfrs7, the DNA replication factors Mcm5 and Brd4, phosphoinositide-3-kinase, annexin A1, mu

17 a structural discontinuity between Mcm2 and Mcm5 and demonstrate that in contrast to other hexameric

18 nd genes known to promote viral replication (MCM5 and EIF3M).

19 an disrupt the interaction between Stat1 and MCM5 and inhibit Stat1 transcriptional activity.

20 lot analyses revealed that the expression of MCM5 and its transcriptional regulator, E2F1, is negativ

21 l II)-mediated transcription is dependent on MCM5 and MCM2 proteins.

22 have shown that MCM2 interacts directly with MCM5 and MCM6; MCM5 with MCM3 and MCM2; and MCM6 with MC

23 We also show that MCM5 and MCM7 are topologically constrained on DNA and t

24 We show that endogenous MCM5 and MCM7 proteins are localized in the nucleus duri

25 tution that compromises its interaction with Mcm5 and the recruitment of Mcm3 and Mcm7 to a replicati

26 lly weakens the interaction between Mcm2 and Mcm5, and Dbf4-Cdc7 phosphorylation of Mcm2 promotes Mcm

27 Disruption of ORC2, MCM5, and HBO1 expression by small interfering RNA reduc

28 P118 is conserved between Mcm3, Mcm4, Mcm5, and Mcm7.

29 urthermore, depletion of Mcm10, Cdc45, Mcm2, Mcm5, and Orc2, respectively, results in aberrant chromo

30 c genes (e.g., MYC, MYBL2, BUB1, MCM2, MCM4, MCM5, and survivin) and up-regulation of several potenti

31 xamer complex and the DNA helicase domain in MCM5 are essential for the process of transcription.

32 nits contact DNA, from MCM2 at the 5'-end to MCM5 at the 3'-end of the DNA spiral, but only MCM6, 4,

33 Furthermore, MCM5 bearing mutations in its ATPase and helicase domain

34 having a mutation corresponding to the yeast MCM5 bob1 mutation.

35 The yeast mcm5-bob1 (P83L) mutation bypasses DDK but results in re

36 tion by DDK, since the defects persist in an mcm5-bob1 background.

37 sed for cells expressing mcm10-m2,3,4 in the mcm5-bob1 background.

38 edicted to interact with P83L suppresses the mcm5-bob1 bypass phenotype.

39 mcm5-bob1 bypasses the growth defect conferred by DDK-ph

40 ting cell cycle delay is intact in cdc7Delta mcm5-bob1 cells, suggesting a direct role for CDC7 in DN

41 xpression of wild-type levels of mcm10-4A in mcm5-bob1 mutant cells resulted in severe growth and DNA

42 We then expressed the mcm10-4A in mcm5-bob1 mutant cells to bypass the defects mediated by

43 chanism to activate origins using the sld3-A mcm5-bob1 mutant that de-regulates the pre-replication c

44 Molecular experiments revealed that the mcm5-bob1 mutation allows for constitutive loading of Cd

45 either Clb5p or Clb2p cyclins suppresses the mcm5-bob1 mutation and prevents bypass.

46 cular analysis of the mechanism by which the mcm5-bob1 mutation bypasses the function of the Cdc7p/Db

47 hly active conformation of Mcm5, whereas the mcm5-bob1 mutation produces a number of conformations, o

48 pressing mcm10-m2,3,4 is not bypassed by the mcm5-bob1 mutation.

49 s, of which only a subset is bypassed by the mcm5-bob1 mutation.

50 A model is proposed in which the Mcm5-bob1 protein assumes a unique molecular conformatio

51 om adoption of these alternate states by the mcm5-bob1 protein can explain both how origin firing occ

52 n of this conserved residue in Mcm5 (P83L of mcm5-bob1) strengthens the interaction between Mcm3 and

53 ynthetic lethality, rad53 mutations suppress mcm5-bob1, a mutation in the replicative MCM helicase th

54 d PFA in vivo was promoted by the suppressor mcm5-bob1, which bypassed DDK requirement, indicating th

55 ued in cells harboring the DDK bypass mutant mcm5-bob1.

56 or CLB5 function in bypass of Cdc7p/Dbf4p by mcm5-bob1.

57 for the direct interaction between Stat1 and MCM5 both in vitro and in vivo.

58 The Mcm5 C-terminus (C5) contacts Orc3 and specifically reco

59 Mcm2, Mcm3, and Mcm5/Cdc46 are conserved proteins essential for the init

60 sive mutation in a member of the MCM family, MCM5/CDC46, which bypasses the requirement for Cdc7p and

61 hase cells containing the CDC7 bypass mutant mcm5/cdc46-bob1.

62 When MCM5 cDNA was reintroduced into fresh TR9-7ER cells, num

63 in the G2 phase and exhibit nuclear Cdc6 and MCM5 co-localization and the absence of geminin.

64 MCM5 containing mutations of R732/K734 did not enhance S

65 lso recovered a viable and fertile allele of mcm5 (denoted mcm5(A7)) that specifically impairs the me

66 e show that homozygotes for a null allele of mcm5 die as third instar larvae, apparently as a result

67 MCM5 directly interacts with the transcription activatio

68 ng Mcm5 subunit stabilises DNA engagement by Mcm5 downstream of the Mcm2 binding site.

69 y, changes in the level of nuclear localized MCM5 during the cell cycle correlated with the changes i

70 Transient over-expression of MCM5 enhanced transcriptional activation by Stat1alpha i

71 tion of human Mcm2 decreases the affinity of Mcm5 for Mcm2, suggesting a potential mechanism for heli

72 while in vivo analysis establishes that Mcm2/Mcm5 gate opening is essential for both helicase loading

73 tions the DNA right in front of the two Mcm2-Mcm5 gates, with each strand being pressed against one g

74 Here we provide a genetic dissection of the mcm5 gene in Drosophila that demonstrates an unexpected

75 e MCM2-7 helicase in vivo by complexing with MCM5 in a manner dependent upon a nuclear-export signal-

76 his novel observation establishes a role for MCM5 in negating the growth arrest function of p53.

77 3 subcomplex through direct interaction with MCM5 in the process of IFN-gamma-induced gene activation

78 that is specifically defective for Mcm3 and Mcm5 interaction (sld3-m10), and also identified a point

79 Crucially, a stable Mcm2/Mcm5 interface is essential for productive ATP-hydrolysi

80 of Mcm2 may open the Mcm2-7 ring at the Mcm2-Mcm5 interface, allowing for single-stranded DNA extrusi

81 7 ring closure, due to mutations at the Mcm2/Mcm5 interface, leads to MCM2-7 ring splitting and compl

82 ntry gate, poised for insertion, at the Mcm2-Mcm5 interface.

83 ediate shows a remodelled, fully-closed Mcm2/Mcm5 interface.

84 the RNA interference technique to show that MCM5 is essential for transcription activation of Stat1

85 These results strongly suggest that MCM5 is recruited through interaction with Stat1alpha in

86 ns of constitutively transcribing genes, and MCM5 is required for transcription elongation of RNA Pol

87 opt a ring shape with a gap between Mcm2 and Mcm5, it is unknown which Mcm interface functions as the

88 primitive cells and myocytes was assessed by MCM5 labeling, myocyte mitotic index, and telomerase fun

89 hronized culture were prepared to detect the Mcm5 loading onto the chromatin in the presence of the w

90 bound throughout the entire S period, while Mcm5 loses chromatin affinity during S phase.

91 re that included CPS1, CTPS2, DARS2, IGFBP3, MCM5, MCM7, NME4, NT5E, PLK1, POLR3G, PTTG1, SERPINB5, T

92 uits a group of nuclear proteins, among them MCM5 (minichromosome maintenance) and MCM3, for transcri

93 A yeast mcm5 mutant with beta-hairpin mutations displays defects

94 y used to analyze a Saccharomyces cerevisiae MCM5 mutant, called BOB1, which contains a single residu

95 m4 mutation is synthetically lethal with the mcm5 mutation.

96 ciation with chromatin and in the loading of Mcm5 onto chromatin origins.

97 tion initiation but not its interaction with Mcm5 or recruitment of the MCM2-7 complex to replication

98 lled minichromosome maintenance deficient 5 (MCM5) or cell division cycle 46 (Saccharomyces cerevisia

99 t mediates the interaction between Stat1 and MCM5; overexpression of this domain can disrupt the inte

100 al substitution of this conserved residue in Mcm5 (P83L of mcm5-bob1) strengthens the interaction bet

101 multiple functions and provide evidence that mcm5 plays a critical role in the meiotic recombination

102 Origin efficiency may result from Mcm5 protein assuming an altered conformation, as predic

103 e, in addition to its known regulatory role, Mcm5 protein has a positive role in origin binding, whic

104 utations in mcm2 and mcm4 cannot bypass DDK, Mcm5 protein may be a unique Mcm protein that is the fin

105 immunoprecipitation (ChIP) analyses that the MCM5 protein, as well as other members of the MCM family

106 In this work, we show that Mcm2, Mcm3, and Mcm5 self-interact and interact with one another to form

107 Antibodies against Cdc6 and Mcm5 stain abnormal cells in cervical smears and section

108 It associates with the regulatory MCM5 subunit of the replicative helicase.

109 Arginine Finger-variant of the neighbouring Mcm5 subunit stabilises DNA engagement by Mcm5 downstrea

110 que DNA entry gate comprised of the Mcm2 and Mcm5 subunits.

111 endometrium in vivo (PLXDC2, COPG1, HSPA12A, MCM5, TBL1XR1, and TTF).

112 tified two specific residues (R732, K734) in MCM5 that are required for the direct interaction betwee

113 ave also identified an independent domain in MCM5 that mediates the interaction between Stat1 and MCM

114 has an active gate between subunits Mcm2 and Mcm5 that opens and closes in response to nucleotide bin

115 ro and in vivo interaction of Stat1alpha and MCM5 were demonstrated.

116 s in a single, highly active conformation of Mcm5, whereas the mcm5-bob1 mutation produces a number o

117 MCM2 interacts directly with MCM5 and MCM6; MCM5 with MCM3 and MCM2; and MCM6 with MCM2 and MCM4.

118 a common site on CMG, including the MCM3 and MCM5 zinc-finger domains.