ライフサイエンスコーパス: CAF-1

1 CAF-1 and each of its individual subunits stably bound t

2 CAF-1 and the Hir proteins operate in distinct but funct

3 CAF-1 binds histones H3 and H4 and deposits histones ont

4 CAF-1 does not protect the genome by assembling it into

5 CAF-1 is also involved in coordinating inheritance of st

6 CAF-1 is essential in human cells for the de novo deposi

7 CAF-1 was a substrate for DNA-dependent protein kinase,

8 CAF-1, Hir proteins, and Asf1 are histone H3/H4 binding

9 CAF-1-depleted cell extracts completely lacked DNA repli

10 CAF-1-mediated resistance to DNA damage is dependent on

11 Chromatin assembly factor 1 (CAF-1) and Rtt106 participate in the deposition of newly

12 somatic cells, chromatin assembly factor 1 (CAF-1) appears to be a key player in assembling new nucl

13 Chromatin assembly factor 1 (CAF-1) assembles nucleosomes in a replication-dependent

14 on 1 (Asf1) and Chromatin Assembly Factor 1 (CAF-1) chaperone histones H3/H4 during the assembly of n

15 perone known as chromatin assembly factor 1 (CAF-1) contributes to transcriptional silencing in yeast

16 he heterotrimer chromatin assembly factor 1 (CAF-1) couples DNA replication to histone deposition in

17 Chromatin assembly factor 1 (CAF-1) deposits histones during DNA synthesis.

18 Chromatin assembly factor 1 (CAF-1) deposits histones H3 and H4 rapidly behind replic

19 stone chaperone Chromatin Assembly Factor 1 (CAF-1) deposits tetrameric (H3/H4)2 histones onto newly-

20 n 1 (Asf1p) and chromatin assembly factor 1 (CAF-1) in global transcriptional regulation in budding y

21 n 1 (Asf1p) and chromatin assembly factor 1 (CAF-1) in vivo.

22 Chromatin assembly factor 1 (CAF-1) is a H3-H4 histone chaperone that associates with

23 Chromatin assembly factor 1 (CAF-1) is a highly conserved protein that functions in D

24 Chromatin assembly factor 1 (CAF-1) is a histone H3-H4 chaperone that deposits newly

25 Chromatin assembly factor 1 (CAF-1) is required for inheritance of epigenetically det

26 Chromatin assembly factor 1 (CAF-1) is the histone chaperone responsible for histone

27 stone chaperone chromatin assembly factor 1 (CAF-1) mediates histone H3-H4 assembly during DNA replic

28 tor 1 (Asf1) to chromatin assembly factor 1 (CAF-1), another histone chaperone that is critical for t

29 ubunit of yeast chromatin assembly factor 1 (CAF-1), as well as upon the karyopherin Kap123p, but was

30 p150 subunit of chromatin assembly factor 1 (CAF-1), forming a multiprotein complex that also contain

31 arge subunit of chromatin assembly factor 1 (CAF-1).

32 n cells lacking chromatin assembly factor 1 (CAF-1).

33 ing mediated by chromatin assembly factor 1 (CAF-1).

34 ysfunctional in chromatin assembly factor-1 (CAF-1) (fas1 and fas2 mutants), which are known to have

35 exes, including chromatin assembly factor-1 (CAF-1) and the Hir proteins .

36 Subunits of the chromatin assembly factor-1 (CAF-1) complex, including Chaf1a and Chaf1b, emerged as

37 Chromatin assembly factor-1 (CAF-1) is a three-subunit protein complex conserved thro

38 for subsequent chromatin assembly factor-1 (CAF-1)-dependent nucleosome assembly.

39 SD-mediated repression and binding to KAP-1, CAF-1 p150, and SP100 but not LBR.

40 ubunit of human chromatin assembly factor 1; CAF-1) bind directly to helix 1 of histone H4, a region

41 he histone acetylation may be required for a CAF-1 independent pathway or function after deposition,

42 reas H3.1 is assembled into nucleosomes in a CAF-1-dependent reaction.

43 chromatin assembly factors (CAFs), Asf1 and CAF-1, in turning off the DNA damage checkpoint in buddi

44 in histone modifications linked to ASF1 and CAF-1-dependent pathways, including SAS-I- and Rtt109p-d

45 l30 mutants with defects linked to ASF1- and CAF-1-dependent pathways.

46 to the chromatin assembly factors Asf1p and CAF-1, we found pol30 mutants did not exhibit a gross de

47 his interaction suggests a role for MBD1 and CAF-1 p150 in methylation-mediated transcriptional repre

48 to investigate interactions between MMR and CAF-1- and ASF1A-H3-H4-dependent histone (H3-H4)2 tetram

49 ulation might be more complex; MutSalpha and CAF-1 interact not only with PCNA, but also with each ot

50 We suggest that PCNA and CAF-1 connect DNA replication to chromatin assembly and

51 The Hir proteins and CAF-1 share a common partner, the highly conserved histo

52 mispair-containing DNA by the MMR system and CAF-1-dependent packaging of the newly replicated DNA in

53 p123p, but was independent of Cac2p, another CAF-1 component, and other chromatin assembly proteins (

54 hanism of histone H3/H4 transfer among Asf1, CAF-1 and DNA from a thermodynamic perspective, we devel

55 During S phase the histone chaperones Asf1, CAF-1, and Rtt106 coordinate to deposit newly synthesize

56 hir1Delta double mutant cells that lack both CAF-1 and HIR complexes than in either single mutant.

57 bstantially defective in the absence of both CAF-1 and Asf1, whereas deleting CAC1 or ASF1 individual

58 Optimal modulation of both CAF-1 and transcription factor levels increased reprogra

59 his complex stimulates histone deposition by CAF-1 .

60 olecular mechanism for histone deposition by CAF-1, a reaction that has remained elusive for other hi

61 tion-coupled nucleosome assembly mediated by CAF-1 and Rtt106.

62 o the DNA-associated tetramer is promoted by CAF-1-induced H3/H4 oligomerization.

63 l )-dependent MMR reactions is suppressed by CAF-1- and ASF1A-H3-H4-dependent deposition of the histo

64 ent Rad21, and the histone chaperone CHAF1A (CAF-1 p150).

65 Mutants in the H3.1 chaperone CAF-1 (fas1-4) maintain a pattern similar to that of wil

66 H3K56 in vivo, whereas the histone chaperone CAF-1 (chromatin assembly factor 1) in humans and Caf1 i

67 molecules are assembled by histone chaperone CAF-1 in a replication-coupled process, whereas H3.3-H4

68 between histone H3-H4 with histone chaperone CAF-1 or Rtt106 increases in cells lacking Rad17.

69 r, our findings reveal the histone chaperone CAF-1 to be a novel regulator of somatic cell identity d

70 s from inactivation of the histone chaperone CAF-1.

71 se data indicate that the histone chaperones CAF-1 and Asf1p regulate the gene expression of a broad

72 The histone chaperones CAF-1 and Rtt106p are required for heterochromatin silen

73 mplexes contain distinct histone chaperones, CAF-1 and HIRA, that we show are necessary to mediate DN

74 s to identify the chromatin assembly complex CAF-1 as a context-specific repressor of Notch signaling

75 plex NURF and the chromatin assembly complex CAF-1.

76 ase requires the histone chaperone complexes CAF-1 (Cac2p, Msi1p and Rlf2p) and RCAF (Asf1p plus acet

77 Here, we have purified a complex containing CAF-1 and H3 and H4 from yeast cells and determined the

78 The mechanisms that enable CAF-1 and other PCNA-binding proteins to function harmon

79 tides are part of the mechanism that enables CAF-1 to function behind replication forks without inter

80 budding yeast deleted for the genes encoding CAF-1 are highly sensitive to double-strand DNA-damaging

81 96 amino acids are dispensable for essential CAF-1 function in vivo.

82 in human MGMT-deficient cell-free extracts, CAF-1-dependent packaging of irreparable O(6)-mG-T mispa

83 d new role for the chromatin assembly factor CAF-1 and the histone-regulating Hir proteins has been d

84 p150 subunit from chromatin assembly factor (CAF-1 p150).

85 of the Drosophila chromatin assembly factor (CAF-1).

86 a subunit of the chromatin assembly factor, CAF-1, and copurifies with the human histone deacetylase

87 not unreplicated, DNA is also competent for CAF-1-dependent chromatin assembly.

88 f both histone H3 and H4 are dispensable for CAF-1-mediated formation of nucleosome cores onto newly

89 y reveal interactions that are essential for CAF-1 function in budding yeast, and importantly indicat

90 r, the data illustrate a clear mechanism for CAF-1-associated H3-H4 chaperone activity in the context

91 e tetramerization, providing a new model for CAF-1-H3/H4 architecture and function during eukaryotic

92 ific acetylation sites are not necessary for CAF-1-dependent nucleosome assembly onto replicated DNA.

93 stones, possibly to maintain opportunity for CAF-1 recruitment and nucleosome assembly.

94 al reporters, overcoming the requirement for CAF-1 in transcriptional silencing.

95 Thus, these studies reveal a novel role for CAF-1 and Rtt106p in epigenetic silencing and indicate t

96 e into chromatin, consistent with a role for CAF-1 in chromatin assembly in vivo.

97 gestion demonstrated that the chromatin from CAF-1 mutant yeast has increased accessibility to these

98 Furthermore, CAF-1 is not required for repair of the DNA per se or fo

99 However, how CAF-1 functions in this process is not yet well understo

100 However, it is unknown how CAF-1 binds and delivers H3-H4 to the DNA.

101 assembly revealed that both dCAF-1 and human CAF-1 mediate chromatin assembly preferentially with pre

102 existence of two PCNA binding sites in human CAF-1, but the defect in PCNA binding had no effect on t

103 re we report that the large subunit of human CAF-1 (p150) contains two distinct PCNA interaction pept

104 The p150 subunit of human CAF-1 contains an N-terminal domain (p150N) that is disp

105 DNA replication in vitro, as seen with human CAF-1.

106 s indicate that, in contrast to yeast, human CAF-1 is necessary for coupling chromatin assembly with

107 ir protein recruitment to the silent loci in CAF-1 mutants, probably as a consequence of the weakened

108 The systematic rDNA loss in CAF-1 mutants leads to the decreased variability of the

109 , termed the HP1BD, which is also present in CAF-1 p150 but not SP100 or LBR.

110 n critical function of the middle subunit in CAF-1.

111 We have found that MutSalpha inhibits CAF-1- and ASF1A-H3-H4-dependent packaging of a DNA mism

112 n replication-coupled nucleosome assembly is CAF-1-dependent histone (H3-H4)2 tetramer deposition, a

113 Cells lacking CAF-1 accumulated in early and mid S-phase and replicate

114 Cells lacking CAF-1 and RCAF are hypersensitive to DNA-damaging agents

115 r proteins are mislocalized in cells lacking CAF-1 and Rtt106p.

116 cus is dramatically reduced in cells lacking CAF-1, Rtt106p, and Sir1p.

117 nous 2mu plasmid is reduced in yeast lacking CAF-1.

118 At the HMR locus, CAF-1 and Rtt106p are required for the initial recruitme

119 The MBD1-CAF-1 p150 interaction requires the methyl-CpG binding d

120 Mechanistically, CAF-1 suppression led to a more accessible chromatin str

121 Unlike Asf1, monomeric CAF-1 binds to multiple H3/H4 dimers, which ultimately p

122 bserved for corresponding mutations in mouse CAF-1.

123 d in eukaryotic cells whereby the ability of CAF-1 to bind DNA is important for its association with

124 to DNA damage is dependent on the ability of CAF-1 to bind PCNA, indicating that PCNA may recruit CAF

125 p48 can bind to histone H4 in the absence of CAF-1 p150 and p60.

126 specific H3-H4 histone chaperone activity of CAF-1.

127 A and, by increasing the binding affinity of CAF-1 and Rtt106 for histone H3, H3K56Ac enhances the ab

128 nd H3K56Ac increases the binding affinity of CAF-1 toward H3-H4 2-fold.

129 arge subunit, Cac1 organizes the assembly of CAF-1.

130 Moreover, the association of CAF-1 with H3 methylated at lysine 79 appeared to occur

131 HIRA to H3.3-H4 and reducing association of CAF-1 with H3.1-H4.

132 Depletion of CAF-1 from various cell lines causes replication fork ar

133 Depletion of CAF-1 in human cell lines demonstrated that CAF-1 was re

134 nd-joining pathways and that the function of CAF-1 during double-strand repair is distinct from that

135 nt chromatin structure, because induction of CAF-1 after DNA damage is sufficient to restore viabilit

136 H4 tetramer and the consequent inhibition of CAF-1-mediated nucleosome formation.

137 Tandem affinity purification of CAF-1-interacting proteins under mild conditions reveale

138 binding had no effect on the recruitment of CAF-1 to chromatin after DNA damage or to resistance to

139 he N terminus is dispensable for the role of CAF-1 in DNA replication- and repair-coupled chromatin a

140 The small subunit of CAF-1 (p48) is a member of a highly conserved subfamily

141 tein Asf1, which binds the middle subunit of CAF-1 as well as to Hir proteins .

142 nds directly to p150, the largest subunit of CAF-1, and the two proteins colocalize at sites of DNA r

143 3 lysine 79, and Cac1p, the large subunit of CAF-1, exhibited a dramatic loss of telomeric silencing

144 ls lacking both Mec1 and the Cac1 subunit of CAF-1.

145 hosphorylation status of the p150 subunit of CAF-1.

146 (CAC), which contains the three subunits of CAF-1 (p150, p60, p48) and H3 and H4, and promotes DNA r

147 Notably, suppression of CAF-1 also enhanced the direct conversion of B cells int

148 lls, and overexpression of the C terminus of CAF-1 p150 prevents the targeting of MBD1 in these cells

149 the association occurs in the C terminus of CAF-1 p150.

150 lines expressing RNAi-resistant versions of CAF-1 and showed that the N-terminal 296 amino acids are

151 tion-independent histone variant H3.3 and on CAF-1 that is specific to the replication-dependent cano

152 d a core histone chaperone (such as NAP-1 or CAF-1) are sufficient for the ATP-dependent formation of

153 Deletion of ASF1 or CAF-1 components led to global transcriptional misregula

154 p150 (p150N) that cannot interact with other CAF-1 subunits is sufficient for maintaining nucleolar c

155 on was reduced approximately 10-fold in RCAF/CAF-1 double mutants.

156 bind PCNA, indicating that PCNA may recruit CAF-1 to sites of double-strand DNA repair.

157 f rDNA copies, and plant lines with restored CAF-1 function (segregated from a fas1xfas2 genetic back

158 cleosome assembly factors, including Rtt106, CAF-1, and lysine residues of H3-H4.

159 A single CAF-1 molecule binds a cross-linked (H3-H4)2 tetramer, o

160 d the function of this domain in stabilizing CAF-1 at replication forks.

161 understand the mechanism of the tri-subunit CAF-1 complex in this process, we investigated the prote

162 Consistent with this idea, we confirm that CAF-1 synchronously binds two H3-H4 dimers derived from

163 CAF-1 in human cell lines demonstrated that CAF-1 was required for efficient progression through S-p

164 We found that CAF-1 suppresses the activity of the MMR system in the c

165 These results highlight that CAF-1 has prominent interactions with the DNA repair mac

166 Together, these data indicate that CAF-1 interacts with H3 methylated at lysine 79 during t

167 These results indicate that CAF-1 mutant yeast globally under-assemble their genome

168 Our genetic analyses indicate that CAF-1 plays a role in both homologous recombination and

169 We propose that CAF-1 has an essential role in assembling chromatin duri

170 proteins under mild conditions revealed that CAF-1 was directly associated with the KU70/80 complex,

171 Our experiments have also revealed that CAF-1- and ASF1A-H3-H4-dependent deposition of the histo

172 Here, we show that CAF-1 and Rtt106p are involved in the early stages of he

173 Here, we show that CAF-1 binds recombinant H3-H4 with 10- to 20-fold higher

174 We show that CAF-1 mutants have a drastic reduction in DNA-bound hist

175 We suggest that CAF-1 and Asf1 function redundantly to deactivate the ch

176 These results suggest that CAF-1 binds to two H3-H4 dimers in a manner that promote

177 These data suggest that CAF-1- and ASF1A-H3-H4-dependent deposition of the histo

178 Taken together, these findings suggest that CAF-1-dependent incorporation of irreparable O(6)-mG-T m

179 Although it has been suggested that CAF-1 is involved in the maintenance of heterochromatin

180 chromatin assembly activity, suggesting that CAF-1 is required for efficient S-phase progression in h

181 c loci in yeast cells deficient for both the CAF-1 and HIR histone H3/H4 deposition complexes, consis

182 of gamma-H2AX does not depend on either the CAF-1 protein, Cac1, or Asf1.

183 Instead, the CAF-1(chromatin assembly factor I) subunit Cac2 level de

184 Here we investigate the CAF-1*H3-H4 binding mode and the mechanism of nucleosome

185 een the yeast CAF-1 subunits, and mapped the CAF-1 domains responsible for H3-H4 binding.

186 that residue substitutions in yAsf1 near the CAF-1/HIRA interface also influence yAsf1's function in

187 interactions with the other subunits of the CAF-1 complex because an N-terminal fragment of p150 (p1

188 tro and altered chromatin association of the CAF-1 large subunit in vivo.

189 genome-scale assays to demonstrate that the CAF-1 and HIR complexes independently stimulate replicat

190 Here we report that the CAF-1 protein complex, an evolutionarily conserved histo

191 so enhances the interaction of Asf1 with the CAF-1 subunit Cac2, H3/H4 forms a tight complex with CAF

192 the protein-protein interactions within the CAF-1-H3/H4 architecture using biophysical and biochemic

193 1 subunit functions as a scaffold within the CAF-1-H3/H4 complex.

194 defective mutants showed reduced binding to CAF-1 in vitro and altered chromatin association of the

195 g DNA and also show reduced binding of H3 to CAF-1, a histone chaperone involved in RC nucleosome ass

196 not Chk2, was phosphorylated in response to CAF-1 depletion, consistent with a DNA replication defec

197 This drives the formation of a transient CAF-1*histone*DNA intermediate containing two CAF-1 comp

198 N-terminally truncated CAF-1 p150 was deficient in proliferating cell nuclear a

199 AF-1*histone*DNA intermediate containing two CAF-1 complexes, each associated with one H3-H4 dimer.

200 Here, we studied whether CAF-1 modulates the activity of the MMR system in the cy

201 ecognition factor MutSalpha, as well as with CAF-1.

202 f Asf1 enhances the interaction of Asf1 with CAF-1.

203 , modifications on H3 and H4 associated with CAF-1 are not known.

204 y, in part, by promoting H3 association with CAF-1 via H3 acetylation.

205 bunit Cac2, H3/H4 forms a tight complex with CAF-1 exclusive of Asf1, with an affinity weaker than As

206 H4 that copurified with CAF-1 was a mixture of isoforms acetylated at lysines 5,

207 Furthermore, Rtt106p interacts with CAF-1 physically through Cac1p.

208 lts define direct structural roles for yeast CAF-1 subunits and uncover a previously unknown critical

209 terminus of Cac1 (Cac1C), a subunit of yeast CAF-1, and the function of this domain in stabilizing CA

210 We show that yeast CAF-1 binding to a H3-H4 dimer activates the Cac1 winged

211 in the direct interaction between the yeast CAF-1 subunits, and mapped the CAF-1 domains responsible