ライフサイエンスコーパス: nibrin

1 and the NBS1 gene product, p95 (NBS protein, nibrin).

2 in DeltaAtm transgenes relative to wild-type nibrin.

3 activation was independent of Mre11-Rad50 or nibrin.

4 in the NBS1 gene, which encodes the protein nibrin.

5 0, which forms a complex with hMre11 and p95/nibrin.

6 pomorphic mutations in the NBN gene encoding nibrin, a component of the MRE11/RAD50/nibrin (MRN) comp

7 nibrin slowed the turnover of phosphorylated nibrin after irradiation, indicating that nuclear export

8 Phosphorylation of nibrin and Chk2 by Atm required Mre11-Rad50 expression i

9 icantly altered the cellular distribution of nibrin and Mre11 and impaired survival after exposure to

10 However, direct interaction between nibrin and Mre11 is required for normal cellular surviva

11 In this study, the interacting domains on nibrin and Mre11 were mapped using the yeast two-hybrid

12 plex of Mre11, Rad50 and NBS1 (also known as nibrin and p95) is important for double-strand break rep

13 1-Rad50 in the activation of Atm and suggest nibrin and/or Mre11-Rad50 also act as adaptors for some

14 from mutations in the NBS1 gene that encodes nibrin, and NBS cells are radiosensitive and defective i

15 However, introduction of anti-Nibrin antibodies into these cells reduced the fidelity

16 Distinct domains of nibrin are required for each of these functions, focus f

17 icient to direct the nuclear localization of nibrin, as well as that of Mre11 and Rad50.

18 To determine whether nibrin-Atm interaction is necessary to stimulate Atm act

19 the nucleus and that this function requires nibrin-Atm interaction.

20 s phosphorylated by Atm, and the Mre11.Rad50.nibrin complex relocalizes to form punctate nuclear foci

21 stimulated by expression of the Mre11/Rad50/nibrin complex.

22 sly, we showed that a C-terminal fragment of nibrin, containing binding sites for both Mre11 and Atm,

23 The N terminus of nibrin contains a forkhead-associated (FHA) domain and a

24 However, this truncated form of nibrin could localize to the nucleus and form radiation-

25 The nibrin DeltaAtm protein interacted with Mre11/Rad50; how

26 fter irradiation in NBS cells expressing the nibrin DeltaAtm transgenes relative to wild-type nibrin.

27 These results indicate that nibrin directs not only the nuclear localization of the

28 n of the carboxy-terminal 101 amino acids of nibrin eliminated its ability to interact with Mre11 and

29 Mutations in the nibrin FHA and BRCT domains did not affect interaction w

30 The NBS1 gene product, p95 (NBS1 or nibrin) forms a complex with Rad50 and Mre11.

31 mine the role of the FHA and BRCT domains in nibrin function, we have performed site-directed mutagen

32 yndrome, which results from mutations in the Nibrin gene, occurs with normal fidelity.

33 unction of the two protein products, Atm and Nibrin, in effecting DNA repair and cell cycle checkpoin

34 In NBS cells, nibrin is absent and Mre11 and Rad50 are cytoplasmic.

35 Nibrin is part of a nuclear multiprotein complex that al

36 In response to radiation, nibrin is phosphorylated by Atm, and the Mre11.Rad50.nib

37 radiation, indicating that nuclear export of nibrin may function, in part, to downregulate posttransl

38 Putative ATM in vitro targets include p95/nibrin, Mre11, Brca1, Rad17, PTS, WRN, and ATM (S440) it

39 cts not only the nuclear localization of the nibrin-Mre11-Rad50 complexes but also radiation-induced

40 on of the radiation-sensitive phenotype, the nibrin-Mre11-Rad50 complexes in these cells were unable

41 The Atm protein kinase and Mre11-Rad50-nibrin (MRN) complex play an integral role in the cellul

42 oding nibrin, a component of the MRE11/RAD50/nibrin (MRN) complex.

43 phorylation of the protein NBS1 (also called nibrin) occurred independently of mismatch repair.

44 to create isogenic cell lines lacking either nibrin or Mre11-Rad50 in the nucleus.

45 isrupted nuclear focus formation and blocked nibrin phosphorylation after irradiation, suggesting tha

46 Despite an effect on nibrin phosphorylation, expression of the FHA or BRCT mu

47 These results indicate that nibrin plays an active role in Atm activation beyond tra

48 The evolutionarily conserved Rad50/Mre11/Nibrin protein complex has a role in DNA double-strand b

49 The Mre11.Rad50.nibrin protein complex plays an essential role in the ma

50 -mediated inhibition of the Rad50, Mre11, or Nibrin proteins reduced the fidelity of signal joint rec

51 In the current study, sequences in mouse nibrin required to direct the nuclear localization of th

52 Mutations in Mre11 and nibrin result in the radiosensitivity disorders ataxia-t

53 sperm protein, Nijmegen breakage syndrome 1 (Nibrin), ribosomal protein L4, Homo sapiens KIAA0419 gen

54 To discriminate whether nibrin's role in Atm activation is to bind and transloca

55 uption of either the NLS or NES sequences of nibrin significantly altered the cellular distribution o

56 Mutation of the NES sequence in nibrin slowed the turnover of phosphorylated nibrin afte

57 t nuclear expression of Mre11-Rad50, but not nibrin, stimulated Atm activation at early times after l

58 of about 95 kDa (p95), which is likely to be Nibrin, the protein encoded by the gene mutated in Nijme

59 e we have taken advantage of this feature of nibrin to create isogenic cell lines lacking either nibr

60 ry to stimulate Atm activation, we expressed nibrin transgenes lacking the Atm binding domain in NBS

61 Unexpectedly, nibrin was found to contain both nuclear localizing sign

62 carboxy-terminal 354-amino-acid fragment of nibrin was sufficient to direct the nuclear localization

63 howed that the C-terminal 100 amino acids of nibrin were necessary and sufficient to translocate the