ライフサイエンスコーパス: MRX

1 MRX also stimulates recruitment of Exo1 and antagonizes

2 ently whenever intravenously infused MBs (3% MRX-801; NuVox) were visualized near the thrombus (n = 1

3 1 cells are not exacerbated by the loss of a MRX protein.

4 light the crucial role of Sae2 in activating MRX cleavage at the correct cell cycle stage.

5 re the role of MRX at telomeres, we analyzed MRX mutants in a de novo telomere addition assay in yeas

6 ase IV appeared at the DSB later than Ku and MRX and in a strongly Ku-dependent manner.

7 Results revealed that Ku and MRX assembled at a DSB independently and rapidly after D

8 ified enzymes in vitro, we found that Ku and MRX regulate the nuclease activity of Exo1 in an opposit

9 lomere and recombination functions of Ku and MRX, confirming that these protein regions are functiona

10 ereas the diploid mutants use the Rad52- and MRX-dependent pathways that repair double strand breaks.

11 We suggest that Top3-Rmi1 and MRX are important for recruitment of the Sgs1-Dna2 compl

12 n a manner that is enhanced by Top3-Rmi1 and MRX.

13 Tel1p, appears to act in the same pathway as MRX: mec1 tel1 cells have telomere phenotypes similar to

14 nhances ATP hydrolysis by MRX and attenuates MRX function in end-tethering, suggesting that Rif2 can

15 feasibility of immunoassays using GMR-based MRX and provides an alternative platform for point-of-ca

16 o found that Rif2 enhances ATP hydrolysis by MRX and attenuates MRX function in end-tethering, sugges

17 but facilitates endonucleolytic scission by MRX with a dependence on ATP and Sae2.

18 otein complexes in Saccharomyces cerevisiae: MRX (Mre11-Rad50-Xrs2), Ku (Ku70-Ku80), and DNA ligase I

19 d53 (Chk2) and recombination protein complex MRX(MRN) inhibit Exo1 in one pathway, whereas in a secon

20 The MRN complex (MRX in yeast) has a direct role in DSB repair and is als

21 i1 complex and the Mre11-Rad50-Xrs2 complex (MRX) have important roles as stimulatory components.

22 We show that the Mre11-Rad50-Xrs2 complex (MRX) initiates 5' degradation, whereas Sgs1 and Dna2 deg

23 ing of both Tbf1 and Rap1 proteins decreases MRX and Tel1 accumulation at nearby DNA ends.

24 Once Tel1 is delocalized, MRX does not associate efficiently with Rap1-covered DNA

25 for the first time, a GMR-based time-domain MRX bioassay.

26 , we systematically investigated time-domain MRX by measuring the signal dependence on the applied fi

27 e brain and is a suitable candidate gene for MRX.

28 In the absence of NHEJ and a functional MRX/N, meiotic DSBs are channeled to EXO-1-dependent HR

29 We present models for how MRX-Sae2 creates entry sites for the long-range resectio

30 The results provide new insights into how MRX catalyses end resection and recombination initiation

31 We identify MRX (Mre11-Rad50-Xrs2) as a positive regulator of this i

32 In MRX, the magnetic nanoparticles (MNPs) are first magneti

33 y, abolition of this exonuclease activity in MRX mutants results in shortened telomeric DNA tracts.

34 ted degradation of DSB ends occurred even in MRX mutants with persistently bound Ku.

35 ubtelomere-binding protein Tbf1 and inhibits MRX localization to DNA ends.

36 collaborates with Rif1 and Rif2 and inhibits MRX localization to DNA ends.

37 hering of Fab fragments to DNA ends inhibits MRX-mediated DNA end processing but enhances Tel1 activa

38 short telomeric TG repeat sequence inhibits MRX accumulation at nearby DNA ends in a Tbf1-dependent

39 d DSBs depended on the presence of an intact MRX complex and ATP binding by Rad50, suggesting a possi

40 t insight into how mutations in a Rho-linked MRX gene may compromise neuronal function.

41 Magnetorelaxometry (MRX) is a promising new biosensing technique for point-o

42 The Mre11-Rad50-Xrs2/Nbs1 (MRX/N) complex orchestrates the cellular response to DSB

43 The Mre11-Rad50-Xrs2/NBS1 (MRX/N) nuclease/ATPase complex plays structural and cata

44 to a DNA gap via the exonuclease activity of MRX, which is stimulated by Sae2 without ATP being prese

45 nt of MRX to the DSB, and other functions of MRX in HR including the recruitment of long-range resect

46 NF orchestrates the recruitment of a pool of MRX that is specifically dedicated to HR.

47 on is accompanied by impaired recruitment of MRX to the DSB, and other functions of MRX in HR includi

48 To further explore the role of MRX at telomeres, we analyzed MRX mutants in a de novo t

49 ding by Rad50, suggesting a possible role of MRX in terminating a NHEJ repair phase.

50 ination assay in yeast to assess the role of MRX in V(D)J joining.

51 ropyridin -1(2H)-yl)phenyl)oxazolidin-2-one (MRX-I), distinguished by its high activity against Gram-

52 ovide a model that indicates how in Rad53 or MRX mutants, an inappropriately active Exo1 may facilita

53 We find that the ability of Sae2 to promote MRX nuclease functions is important for DNA damage survi

54 These data indicate that Tel1 promotes MRX retention to DSBs and this function is important to

55 The role of Tel1 in promoting MRX accumulation to DSBs is counteracted by Rif2, which

56 d this function is important to allow proper MRX-DNA binding that is needed for end-tethering and DSB

57 tethering, suggesting that Rif2 can regulate MRX activity at DSBs by modulating ATP-dependent conform

58 Nonsyndromic X-linked mental retardation (MRX) syndromes are clinically homogeneous but geneticall

59 in nonspecific X-linked mental retardation (MRX), three encode regulators or effectors of the Rho GT

60 n implicated in X-linked mental retardation (MRX).

61 The DNA damage sensor MRX is required for histone loss, which also depends on

62 ncluding Ku, RPA, and nucleosomes, stimulate MRX-Sae2 endonuclease cleavage in vitro.

63 Here, we show that MRX recruits Dna2 nuclease to DSB ends.

64 the absence of histone loss, suggesting that MRX-dependent nucleosome remodelling regulates the acces

65 section by the Top3-Rmi1 heterodimer and the MRX proteins is by complex formation with Sgs1, which un

66 ble-strand breaks (DSBs) is initiated by the MRX/MRN complex (Mre11-Rad50-Xrs2 in yeast; Mre11-Rad50-

67 nd Xrs2p proteins form a complex, called the MRX complex, that is required to maintain telomere lengt

68 Rad50 and Xrs2 proteins and thereby for the MRX complex in promoting PRR via both the Rad5 and Rad52

69 n, we showed an absolute requirement for the MRX complex in signal joining, suggesting that the Mre11

70 nd protection by Ku, the requirement for the MRX complex is bypassed and resection is executed by Exo

71 In Caenorhabditis elegans, evidence for the MRX/N role in DSB resection is limited.

72 olecular events leading to a switch from the MRX/Sae2-dependent initiation to the Exo1- and Dna2-depe

73 Several proteins, including the MRX/N complex, Tel1/ATM (ataxia telangiectasia mutated),

74 In exo1Deltasgs1Delta double mutants, the MRX complex together with Sae2 nuclease generate, in a s

75 Here we report that loss of the MRX (Mre11p, Rad50p, Xrs2p) and Ku70/80 (Ku70p, Ku80p) c

76 In contrast, Mre11 protein, part of the MRX complex, accumulates at unresected DSB ends.

77 Among these were subunits of the MRX complex, which forms a molecular structure similar t

78 for the telomerase-promoting activity of the MRX complex.

79 Mre11 is one member of the MRX/N (Mre11, Rad50, and Xrs2/Nbs1) complex required for

80 letions arise in yeast, and suggest that the MRX and Ku70/80 complexes are partially redundant in mit

81 Further investigation indicated that the MRX complex did not contribute to metaphase cohesion ind

82 from this model system, we propose that the MRX complex helps to prepare telomeric DNA for the loadi

83 Rather, the data suggest that the MRX complex is involved in recruiting telomerase activit

84 We found that the MRX genes were absolutely required for telomerase-mediat

85 ng in the absence of Ku and Sae2 or when the MRX complex is intact, but functionally compromised by e

86 These data rule out models in which the MRX complex is necessary for Cdc13p binding to telomeres

87 Cdc13p binding to telomeres or in which the MRX complex is necessary for the catalytic activity of t

88 l1 is activated through interaction with the MRX complex and DNA ends.

89 e revealed all known interactions within the MRX, Ku, and DNA ligase IV complexes, as well as three a

90 Cells lacking any one of the three MRX proteins and Mec1p, an ATM-like protein kinase, unde

91 Thus, MRX may regulate two pathways of chromatin changes: nucl

92 at the MR complex has equivalent activity to MRX in cleavage of protein-blocked DNA ends.

93 r, how mutations in Rho-linked genes lead to MRX.

94 or palindromic DNA structure susceptible to MRX-Sae2, and internal protein blocks also trigger DNA c

95 -stranded DNA in vitro relative to wild-type MRX, consistent with the increased turnover of Mre11 fro

96 In vivo, MRX is required for a 5' --> 3' exonuclease activity tha

97 These results support a model in which MRX controls Tel1 activation by recognizing protein-boun

98 ein that is absent in a family affected with MRX, is required for dendritic spine morphogenesis.

99 charomyces cerevisiae Sae2 can function with MRX to initiate 5'-3' end resection and also plays an im

100 ted individuals in a multiplex pedigree with MRX (MRX30), previously mapped to Xq22, show a point mut

101 The budding yeast Mre11-Rad50-Xrs2 (MRX) complex and Sae2 function together in DNA end resec

102 The yeast Mre11-Rad50-Xrs2 (MRX) complex and Sae2 function together to initiate DNA

103 joining component, and the Mre11-Rad50-Xrs2 (MRX) complex and Sae2, end-processing factors crucial fo

104 In budding yeast, the Mre11-Rad50-Xrs2 (MRX) complex associates with DNA ends and promotes check

105 iated by the action of the Mre11-Rad50-Xrs2 (MRX) complex to direct repair toward HR.

106 e Saccharomyces cerevisiae Mre11-Rad50-Xrs2 (MRX) complex, the Sgs1-Top3-Rmi1 complex, Dna2 protein a

107 ation of Tel1, but not the Mre11-Rad50-Xrs2 (MRX) complex, to adjacent DNA ends.

108 inding at DNA ends via the Mre11-Rad50-Xrs2 (MRX) complex.

109 -Nej1 (DNA ligase IV), and Mre11-Rad50-Xrs2 (MRX).

110 requires several enzymes; Mre11/Rad50/Xrs2 (MRX) and Sae2 are implicated in the onset of 5'-strand r

111 k restart pathway, and the MRE11/RAD50/XRS2 (MRX) complex were critical for viability of rrm3 cells.

112 e of Sae2 is linked to the Mre11/Rad50/Xrs2 (MRX) complex, which is important for the processing of D

113 n, Ku, and the HR protein, Mre11/Rad50/Xrs2 (MRX) complex.

114 nents of the homologous Mre11p-Rad50p-Xrs2p (MRX) complex are viable.

115 accharomyces cerevisiae Mre11p/Rad50p/Xrs2p (MRX) complex is evolutionarily conserved and functions i

116 erevisiae: the Ku heterodimer (Yku70-Yku80), MRX (Mre11-Rad50-Xrs2), and DNA ligase IV (Dnl4-Lif1), a