ライフサイエンスコーパス: MCM3

1 We report the cloning of fission yeast mcm3 +.

2 associate with Mcm2-7 via interactions with Mcm3.

3 whose action is mediated by interaction with MCM3.

4 n bind to chromatin through interaction with MCM3.

5 We have characterized two mutant alleles, mcm3-1 and mcm3-10, in Saccharomyces cerevisiae and show

6 Mcm3-1 contains a G246E mutation that diminishes the eff

7 t Mcm3-10 is defective in a step before, and Mcm3-1 is defective in a step after the recruitment of t

8 ynthetically lethal with orc2-1, mcm2-1, and mcm3-1.

9 Mcm3-10 contains a P118L substitution that compromises i

10 These observations indicate that Mcm3-10 is defective in a step before, and Mcm3-1 is def

11 characterized two mutant alleles, mcm3-1 and mcm3-10, in Saccharomyces cerevisiae and showed that the

12 ubiquitination by uba1-165, a suppressor of mcm3-10, restored the interaction of Mcm3-10p with subun

13 ssor of mcm3-10, restored the interaction of Mcm3-10p with subunits of the MCM complex and its recrui

14 dimer of the Mcm4/6/7 heterotrimer, and the Mcm3/5 heterodimer.

15 ic core of the Mcm complex and that Mcm2 and Mcm3/5 may be involved in the regulation of the activity

16 e results, the interaction of either Mcm2 or Mcm3/5 with the Mcm4/6/7 complex resulted in the disasse

17 suggested that Mcb1 interacts robustly with Mcm3-7 but not Mcm2.

18 Study of the Mcm3/7p ATPase shows that an essential arginine in Mcm3p

19 s connects the remaining MCM proteins to the Mcm3/7p pair.

20 of the minichromosome maintenance protein 3 (MCM3), a component of the hexameric MCM DNA helicase.

21 perm chromatin but do prevent association of MCM3, a protein essential for replication.

22 fect MCM2-7 dynamics or function rather than MCM3 abundance.

23 MCM3 acetylase (MCM3AP) and germinal-centre associated n

24 These results indicate that MCM3 acetylase activity of MCM3AP is required to inhibit

25 therefore confused in databases because the MCM3 acetylase DNA sequence is contained entirely within

26 MCM3 acetylating protein, MCM3AP, binds and acetylates M

27 mRNA export factor Sac3p, and the mammalian MCM3 acetyltransferase.

28 Second, MCM3 acts as a negative regulator of the MCM2-7 helicase

29 ation of KEAP1-interacting proteins revealed MCM3, an essential subunit of the replicative DNA helica

30 All three DNA polymerases, Mcm3 and Cdc45, but not Orc2, still formed complexes in

31 include several proteins (Sld2, Cdc6, Orc6, Mcm3 and Cdh1) involved in early S-phase events.

32 lating protein, MCM3AP, binds and acetylates MCM3 and inhibits cell cycle progression.

33 racts directly with MCM5 and MCM6; MCM5 with MCM3 and MCM2; and MCM6 with MCM2 and MCM4.

34 We also show that interaction between MCM3 and MCM3AP is essential for nuclear localization an

35 m5-bob1) strengthens the interaction between Mcm3 and Mcm5 and allows cells to enter S phase independ

36 n of Sld3 that is specifically defective for Mcm3 and Mcm5 interaction (sld3-m10), and also identifie

37 interaction with Mcm5 and the recruitment of Mcm3 and Mcm7 to a replication origin.

38 ow that members of the replicative helicase (Mcm3 and Mcm7) play a role in silencing and physically i

39 Orc2, Mcm3, and DUE-B were also bound at an ectopic c-myc repl

40 In this work, we show that Mcm2, Mcm3, and Mcm5 self-interact and interact with one anoth

41 Mcm2, Mcm3, and Mcm5/Cdc46 are conserved proteins essential fo

42 leotide reductase 2, thymidylate synthetase, MCM3, and MCM7 genes, but actin RNA was not affected.

43 Similarly, the signals from Orc1, Mcm3, and Mcm7 were at background levels in cells arrest

44 f Rb-E2F-regulated genes cyclin A, cyclin E, MCM3, and PCNA are also elevated.

45 e sites of KEAP1-dependent ubiquitylation in MCM3, and these sites are on predicted exposed surfaces

46 of the origin recognition complex, ORC, and MCM3, another member of the MCM family.

47 Mcm2 and Mcm3 are abundant proteins, present in approximately 4 X

48 ns for KEAP1 within the nucleus and identify MCM3 as a novel substrate of the KEAP1-CUL3-RBX1 E3 liga

49 The results reported establish that MCM2 and MCM3 assemble into homohexamers and exhibit DNA binding,

50 we now demonstrate that CDK1 phosphorylates MCM3 at Ser-112, Ser-611, and Thr-719.

51 treatment, the inhibitory phosphorylation of MCM3 at Ser-205 was reduced, and this reduction was acco

52 lteration of chromatin structure and loss of Mcm3 binding.

53 minichromosome maintenance complex protein, MCM3, bound TR in late-G(1)/S-arrested cells, which coin

54 el qualitative change in the distribution of Mcm3, but not Orc2, across the c-myc replicator.

55 ivation through the novel phosphorylation of MCM3 by Chk1.

56 forms and that distinct isoforms of Mcm2 and Mcm3 can be detected at specific stages of the cell cycl

57 Mcm3-deficient erythroblasts display aberrant DNA replic

58 3 + is essential and spores carrying a Delta mcm3 disruption arrest with an apparently replicated DNA

59 In vitro binding assays indicate that MCM3 does not interact directly with Stat1, suggesting t

60 , preferentially controls the sumoylation of Mcm3 during DNA replication.

61 g them MCM5 (minichromosome maintenance) and MCM3, for transcription activation.

62 iability, but all attempts to delete TK1620 (MCM3) have been unsuccessful arguing that that MCM3 is e

63 with Stat1, suggesting that the presence of MCM3 in the group of Stat1TAD-interacting proteins is du

64 ated the carboxyl termini of mMCM3 and human MCM3 in vivo and the phosphorylated form of MCM3 retaine

65 MCM3 inhibits transactivation domain function, whereas M

66 We also show that S. cerevisiae Mcm3 is a phosphoprotein that exists in multiple isoform

67 KEAP1 targeting motif in MCM3 suggests that MCM3 is a point of direct contact between KEAP1 and the

68 Mcm3 is a subunit of the hexameric MCM2-7 complex requir

69 M3) have been unsuccessful arguing that that MCM3 is essential and is likely the replicative helicase

70 We show that MCM3 is ubiquitylated by the KEAP1-CUL3-RBX1 complex in

71 mcm3 + is essential and spores carrying a Delta mcm3 dis

72 but that ATM is the predominant UV-activated MCM3 kinase in vivo.

73 osome remodeling, histone deacetylation, and MCM3 loading at DS.

74 1, coinciding with nucleosome remodeling and MCM3 loading, and preceding the onset of DNA replication

75 at the carboxyl terminus of chromatin-loaded MCM3 may be sequestered from ATM-dependent checkpoint si

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

77 prereplication complex proteins Orc1, Orc2, Mcm3, Mcm7, and Cdc6 and the novel DNA unwinding element

78 In G(1)-arrested HeLa cells, Mcm3, Mcm7, and DUE-B were prominent near the DUE, while

79 Ser-732) in the carboxyl terminus of murine MCM3 (mMCM3) and that ATM phosphorylates both sites in v

80 Remarkably, the Mcm2-Mcm3 NLS and the Mcm3 NES are sufficient to form a transport module that

81 Remarkably, the Mcm2-Mcm3 NLS and the Mcm3 NES are sufficient to form a trans

82 nuclear export signal (NES) adjacent to the Mcm3 NLS.

83 id maintenance and increase EBNA1, ORC2, and MCM3 occupancy at OriP.

84 First, ATM phosphorylates MCM3 on S535 in response to ionizing radiation.

85 x undergoes dephosphorylation, and the Mcm2, Mcm3, or Mcm6 subunits are then actively phosphorylated

86 horylation sites are conserved in vertebrate MCM3 orthologs suggesting that this motif may serve impo

87 These data reveal that CDK-dependent MCM3 phosphorylation contributes to the regulated format

88 d ATR jointly contribute to UV light-induced MCM3 phosphorylation, but that ATM is the predominant UV

89 romotes net export by phosphorylation of the Mcm3 portion of this module and that nuclear export of t

90 etermined that KEAP1 does not regulate total MCM3 protein stability or subcellular localization.

91 The rest of the Mcm2 and Mcm3 proteins are disturbed to both the cytoplasm and nu

92 was related to the time when Orc1, Orc2 and Mcm3 proteins became stably bound to hamster chromatin.

93 s redundancy, we see multiple sites bound to MCM3 (representative of the helicase) in the region flan

94 MCM3 in vivo and the phosphorylated form of MCM3 retained association with the canonical MCM complex

95 Here we report that Chk1 phosphorylates the MCM3 subunit of the MCM complex at Ser-205 under normal

96 Our analysis of a KEAP1 targeting motif in MCM3 suggests that MCM3 is a point of direct contact bet

97 lear localization signals (NLSs) on Mcm2 and Mcm3 that are each necessary, but not sufficient, for nu

98 ential, conserved carboxy-terminal domain of Mcm3 that interacts with and stimulates the ATPase activ

99 Importantly, we find that MCM3 that is prebound to chromatin does not dissociate w

100 ffect steady-state levels of chromatin-bound MCM3, the ATM-phosphorylated form of MCM3 was preferenti

101 9 degrees N MCM3, the proposed replicative helicase, unwinds DNA at

102 icate that only a small fraction of Mcm2 and Mcm3 tightly associates with chromatin, from late M phas

103 Mutating the Ser-205 of MCM3 to Ala increased the length of DNA replication trac

104 Strikingly, loss of MCM3 triggers the destabilization of other MCM proteins,

105 n-bound MCM3, the ATM-phosphorylated form of MCM3 was preferentially localized to the soluble, nucleo

106 Orc1 and Mcm3 were easily eluted from chromatin during mitosis an

107 MCM7 and MCM3 were identified as cyclin D1-binding proteins.

108 emporally correlated with that of endogenous MCM3 when cells were released from mitosis.

109 and further examine one replication protein, Mcm3, where a cluster of consensus sites near a nucleocy

110 complexes with the same kinetics as MCM7 and MCM3, where they associated specifically with MCM7.

111 acting proteins is due to the association of MCM3 with MCM5.

112 rylation of Ser-112 triggers the assembly of MCM3 with the remaining MCM subunits and subsequent chro