ライフサイエンスコーパス: FANCG

1 FANCG has been shown to contain seven tetratricopeptide

2 FANCG interacted with one of these regions and specifica

3 FANCG is a part of the FA core complex that is responsib

4 FANCG(S7A) aberrantly localized to globules in chromatin

5 ANCC (3), FANCD1 (1), FANCD2 (3), FANCF (2), FANCG (2), FANCI (1), FANCJ (2), and FANCL (3).

6 S387A mutant abolished FANCG fusion protein phosphorylation by cdc2.

7 recipitated with BRCA2 from human cells, and FANCG co-localized in nuclear foci with both BRCA2 and R

8 FANCA and FANCG are dispensable for maximal in vitro ubiquitinatio

9 Here we show that FANCA and FANCG are redox-sensitive proteins that are multimerized

10 interaction studies indicated that FANCA and FANCG bind directly to mu-calpain.

11 multimerization and interaction of FANCA and FANCG in vitro.

12 triggers the multimeric complex of FANCA and FANCG in vivo but also induces the interaction between F

13 The FANCA and FANCG proteins deficient in FA groups A and G interact d

14 Both FANCA and FANCG proteins exist as monomers under non-oxidizing con

15 current study, mutant forms of the FANCA and FANCG proteins have been generated and analyzed with res

16 Similar immunolocalization for FANCA and FANCG suggested that these proteins interact in vivo.

17 r results lead us to conclude that FANCA and FANCG uniquely respond to oxidative damage by forming co

18 All exons of FANCA and FANCG were sequenced, and no mutations were found.

19 We find that both the upstream (FANCA and FANCG) and downstream (FANCD2) FA pathway components pro

20 the other cloned FA gene products (FANCA and FANCG) remain unknown.

21 n of FANCA restored levels of both FANCA and FANCG, whereas overexpression of FANCG or FANCC did not

22 tween the localization patterns of FANCA and FANCG.

23 so induces the interaction between FANCA and FANCG.

24 ker interaction of FANCE with both FANCA and FANCG.

25 Human cells deficient in FANCC and FANCG are also hypersensitive to plasma levels of formal

26 FANCC and FANCG disruption abrogated FANCD2 monoubiquitination, co

27 FANCC and FANCG disruption also resulted in increased clastogenic

28 interstrand-cross-linking agents, FANCC and FANCG disruption caused increased clastogenic damage, G2

29 Finally, FANCC and FANCG disruption increased spontaneous chromosomal break

30 We endogenously disrupted FANCC and FANCG in a human adenocarcinoma cell line and determined

31 The recent identification of FANCC and FANCG mutations in resected pancreatic tumors selected f

32 To further assess the relevance of FANCC and FANCG mutations to pancreatic cancer we conducted a muta

33 inherited and somatic mutations of FANCC and FANCG present in young-onset pancreatic cancer.

34 its effector RAD51 and the FANCA, FANCC and FANCG proteins.

35 ently, several sequence changes in FANCC and FANCG were reported in pancreatic cancer.

36 coimmunoprecipitates with FANCA, FANCC, and FANCG but not with FANCD2.

37 rescent-tagged versions of FANCA, FANCC, and FANCG colocalize in cytoplasm and nucleus, chiefly in ch

38 Given that FANCA, FANCC, and FANCG complementation groups account for more than 90% o

39 BM cells, mutations in the FANCA, FANCC, and FANCG genes markedly increase the amount of PKR bound to

40 d cross-links and that the FANCA, FANCC, and FANCG proteins are bound to this damaged DNA as well.

41 minimally dependent on the FANCA, FANCC, and FANCG proteins, does not require FANCD2.

42 al interaction of at least FANCA, FANCC, and FANCG, and possibly of other FA and non-FA proteins.

43 ow that three FA proteins, FANCA, FANCC, and FANCG, functionally interact with the PKR kinase, which

44 he Fanconi anemia proteins FANCA, FANCC, and FANCG.

45 3 of the encoded proteins, FANCA, FANCC, and FANCG/XRCC9, interact in a multisubunit protein complex.

46 e of the encoded proteins, FANCA, FANCC, and FANCG/XRCC9, interact in a nuclear complex, required for

47 emia (FANCA, FANCC, FANCD2, FANCE, FANCF and FANCG) as well as BRCA1 and BRCA2 (FANCD1).

48 o determine whether FANCA, FANCC, FANCF, and FANCG directly interact with ERCC1 and XPF and, if so, t

49 plex containing the FANCA, FANCC, FANCF, and FANCG proteins is required for the activation of the FAN

50 cts (FANCA, FANCC, FANCD2, FANCE, FANCF, and FANCG proteins) interact in a common pathway.

51 nes (FANCA, FANCC, FANCD2, FANCE, FANCF, and FANCG).

52 uding FRA1, ETV4, MCM2, AXL, MT3, TRAP1, and FANCG), whereas 36 genes (including IGFBP3, TRAM1, and K

53 This binding between FANCG and the ERCC1-XPF endonuclease, combined with our

54 ved C-terminal site in BRCA2 that also binds FANCG/XRCC9.

55 arboxy-terminal leucine zipper region, bound FANCG in the cytoplasm.

56 ort, we demonstrate that the recently cloned FANCG/XRCC9 protein is required for binding of the FANCA

57 The molecular mass of cytoplasmic FANCA, FANCG, FANCC, and nuclear FANCD2 were normal.

58 xhibited a marked decrease in nuclear FANCA, FANCG, and FANCD2-L.

59 These results demonstrate that FANCA-FANCG complexes are required for cellular resistance to

60 toplasm, we suggest that FANCC and the FANCA-FANCG complexes suppress MMC cytotoxicity within distinc

61 G complementary DNA (cDNA) resulted in FANCA/FANCG binding, prolongation of the cellular half-life of

62 On the basis of 2-hybrid analysis, the FANCA/FANCG binding is a direct protein-protein interaction.

63 These results demonstrate that the FANCA/FANCG interaction is required to maintain the cellular l

64 FANCA, FANCC, FANCG, and FANCF proteins form a multisubunit nuclear co

65 FA-binding proteins, including FANCA, FANCC, FANCG, cdc2, and GRP94, thus validating the approach.

66 elected mutations in DNA repair genes FANCC, FANCG and BRCA2 respectively, were less sensitive to MK-

67 crete complex comprising FANCD1/BRCA2-FANCD2-FANCG-XRCC3 (D1-D2-G-X3).

68 ificantly reduced MMC sensitivity but FANCF, FANCG, and FANCC did not.

69 proteins (FANCA, FANCB, FANCC, FANCE, FANCF, FANCG and FANCL) form a nuclear Fanconi anemia core comp

70 The FA proteins FANCA, FANCC, FANCE, FANCF, FANCG, and FANCL participate in a core complex.

71 FANCB, FANCC, FANCD1, FANCD2, FANCE, FANCF, FANCG, and FANCL), and identified orthologs in the genom

72 FANCB, FANCC, FANCD1, FANCD2, FANCE, FANCF, FANCG, FANCI, FANCJ, FANCL, FANCM, and FANCN).

73 that the amino terminal two-thirds of FANCG (FANCG amino acids 1-428) binds to the amino terminal nuc

74 region of the FANCA protein is required for FANCG binding, FANCC binding, nuclear localization, and

75 Furthermore, FANCG could be co-immunoprecipitated with BRCA2 from hum

76 We demonstrate that the FA group G (FANCG) protein is found in mitochondria.

77 er, Fanconi anemia complementation group G- (FANCG-) and FANCC-deficient pancreatic tumor lines were

78 he in vivo role of one of these human genes (FANCG), we generated a targeted disruption of murine Fan

79 Human FANCG complemented these cells, whereas human FANCG(S7A)

80 ANCG complemented these cells, whereas human FANCG(S7A) did not.

81 Phosphorylation of serine 7 in FANCG is functionally important in the FA pathway.

82 The site of interaction in FANCG was mapped to a motif that binds to SH3 domains an

83 rrest, and DNA damage repair genes including FANCG, FOXO3A, GADD45A, GADD45B, and GADD45G.

84 Eight of the FA proteins, including FANCG, participate in a nuclear core complex that is req

85 expression of FANCA mutants encoding intact FANCG interaction domains induced hypersensitivity to MM

86 n of FANCA was abolished by mutations in its FANCG-binding domain.

87 Wild-type but not G546R mutant FANCG physically interacts with the mitochondrial peroxi

88 A characteristic matching of FANCC-null, FANCG-null, BRCA2/FANCD1-null, and PALB2/FANCN-null phen

89 ot sufficient for the functional activity of FANCG.

90 We propose that this binding of FANCG to alphaIISp may be important for the stability of

91 PRs 1, 3, 5, and 6 are needed for binding of FANCG to ERCC1.

92 r, these results demonstrate that binding of FANCG to the amino terminal FANCA NLS sequence is necess

93 current study the functional consequences of FANCG/FANCA binding were examined.

94 o noncontiguous carboxyl-terminal domains of FANCG encompassing amino acids 400-475 and 585-622.

95 n human and hamster cells that expression of FANCG protein, but not the other core complex proteins,

96 Moreover, at least one function of FANCG and FANCA is to regulate the nuclear accumulation

97 a 14-kDa fragment of the C-terminal half of FANCG.

98 we show that loss of the murine homologue of FANCG (Fancg) results in a defect in MSPC proliferation

99 Mapping the sites of interaction of FANCG with ERCC1, using site-directed mutagenesis, demon

100 th a reciprocal increase in the half-life of FANCG.

101 h FANCA and FANCG, whereas overexpression of FANCG or FANCC did not restore FANCA levels.

102 83 and S387 abolished the phosphorylation of FANCG at mitosis.

103 The phosphorylation of FANCG at serine 7 by using mass spectrometry was previou

104 We also show that phosphorylation of FANCG serine 7 is required for its co-precipitation with

105 tudy was to map the phosphorylation sites of FANCG at mitosis and to assess their functional importan

106 no acid sequences at the carboxy terminus of FANCG are required for the binding of FANCC in the compl

107 strate that the amino terminal two-thirds of FANCG (FANCG amino acids 1-428) binds to the amino termi

108 clastogenic damage on irradiation, but only FANCG disruption caused a subsequent decrease in relativ

109 tion events for core complex member proteins FANCG and FANCA by phosphorylation.

110 lts demonstrate that one of the FA proteins, FANCG, contains a motif that interacts directly with the

111 One of these FA proteins, FANCG, was found to have a strong affinity for ERCC1 and

112 We show that in an in vitro kinase reaction FANCG is radioactively labeled.

113 lls that fail to express either phospho-Ser7-FANCG, or full length BRCA2 protein, lack the interactio

114 These results argue that FANCG has a role independent of the FA core complex, and

115 epair (HRR) is supported by our finding that FANCG and the RAD51-paralog XRCC3 are epistatic for sens

116 We found that FANCG was capable of binding to two separate sites in th

117 ed with our previous studies which show that FANCG is involved in the incision step mediated by ERCC1

118 ion sequence (NLS) of FANCA, suggesting that FANCG plays a role in regulating FANCA nuclear accumulat

119 The FANCG protein binds directly to the amino terminal nucle

120 cates that FA patients with mutations in the FANCG gene and patients homozygous for null mutations in

121 Moreover, the FANCG protein is a component of a nuclear protein comple

122 nterestingly, a truncated mutant form of the FANCG protein, lacking the carboxy terminus, binds in a

123 ch is associated with phosphorylation of the FANCG protein.

124 We and others have reported that the FANCG protein (Fanconi complementation group G) is phosp

125 in Chinese hamster ovary cells in which the FANCG homologue is mutant.

126 Correction of an FA-G cell line with the FANCG complementary DNA (cDNA) resulted in FANCA/FANCG b

127 lu(7) appeared to be critical for binding to FANCG.

128 the previously described binding of FANCA to FANCG, we now demonstrate direct interaction of FANCF wi

129 ve candidate tumor suppressor genes (TOPORS, FANCG, RAD51, TP53BP1, and BIK) that could have a role i

130 truncating FANCC mutations but no truncating FANCG mutations were identified in young onset (<55 year

131 Only wild-type FANCG cDNA fully corrected FA-G mutant cells.

132 We also tested the effect of human wild-type FANCG in Chinese hamster ovary cells in which the FANCG

133 Unexpectedly, FANCG(S7A) bound to and stabilized the endogenous forms

134 The FA pathway, of which FANCG is a part, is highly regulated by a series of phos

135 demonstrate direct interaction of FANCF with FANCG, of FANCC with FANCE and a weaker interaction of F

136 ERCC1, in turn, was shown to interact with FANCG via its central domain, which is different from th