ライフサイエンスコーパス: MSH3

1 nuclear export signals (NES1 and -2) within MSH3.

2 to domain I of Msh2; none have been found in MSH3.

3 for nuclear localization within full-length MSH3.

4 PF recruitment to Z-DNA is dependent on MSH2-MSH3.

5 the requirements for mispair interaction by Msh3.

6 r in that Top1 removal does not require Msh2-Msh3.

7 ditional DNA mismatch repair genes, MSH6 and MSH3.

8 mutations in the Apc gene were suppressed by Msh3.

9 lso on the mismatch repair proteins Msh2 and Msh3.

10 d by the msh2 mutation and about 100-fold by msh3.

11 nhances the mismatch binding ability of MSH2-MSH3.

12 nd encodes an aminoacid change (Pro67Ala) in MSH3.

13 rmline mutations in the mismatch-repair gene MSH3.

14 cleotide binding and/or exchange within Msh2-Msh3.

15 pect to the position of the bound ATP within Msh3.

16 fluorescence imaging to investigate how Msh2-Msh3, a eukaryotic mismatch repair complex, navigates on

17 In the other, Msh2-Msh6 or Msh2-Msh3 activate the MutL homolog 1 (Mlh1)-postmeiotic segr

18 Huntington's disease cohort found increased MSH3 and DHFR expression are associated with disease pro

19 und that repeat variants are associated with MSH3 and DHFR expression.

20 Mispair binding analysis with purified Msh2-Msh3 and DNA substrates derived from CAN1 sequences foun

21 titive DNA sequences is coincident with MSH2-MSH3 and is decreased in Msh2-/- and Msh3-/- mice, sugge

22 ond complex involves MLH3 together with MSH2-MSH3 and localizes to repetitive sequences at centromere

23 us for mutations at the Msh3, Msh2, and both Msh3 and Msh2 loci (2).

24 DSB-induced gene conversion differently from msh3 and msh2, which are also defective in removing nonh

25 Msh2-Msh3 and Msh2-Msh6 are two partially redundant mispair-r

26 These data indicate that eukaryotic Msh2-Msh3 and Msh2-Msh6 complexes are targets for inhibition

27 h3 and performed a comparative study of Msh2-Msh3 and Msh2-Msh6 for mispair binding, sliding clamp fo

28 n of function phenotype with respect to MSH2-MSH3 and MSH2-MSH6 functions.

29 epair with either MSH3 or MSH6, and the MSH2-MSH3 and MSH2-MSH6 heterodimers have a role in the recog

30 humans have indicated a requirement for MSH2-MSH3 and MSH2-MSH6 heterodimers in mismatch recognition.

31 In eukaryotes the MSH2-MSH3 and MSH2-MSH6 heterodimers initiate mismatch repair

32 Our studies contrast how Msh2-Msh3 and Msh2-Msh6 navigate on a crowded genome and sugg

33 the ATPase domain is conserved between Msh2-Msh3 and Msh2-Msh6.

34 c protein complexes of MutS homologues, MSH2-MSH3 and MSH2-MSH6.

35 with mispair-binding protein complexes, MSH2.MSH3 and MSH2.MSH6, and that PCNA enhances MSH2.MSH6 mis

36 mmon in HNPCC families, whereas mutations in MSH3 and MSH6 are rare.

37 We have conducted a comparative analysis of Msh3 and Msh6 deficiency in mouse intestinal tumorigenes

38 t cells harboring null mutations in both the MSH3 and MSH6 genes exhibit microsatellite instability a

39 een observed in the TGFbetaRII, BAX, IGFIIR, MSH3 and MSH6 genes in colon and other cancers.

40 utational spectra and clarified the roles of Msh3 and Msh6 in DNA repair and intestinal tumorigenesis

41 Thus, MSH3 and MSH6 interactions with PCNA may facilitate earl

42 ns similarly, analyses of reversion rates in msh3 and msh6 mutants revealed distinct specificities of

43 MSH3 and MSH6 peptides containing these motifs bound PCN

44 The mismatch repair components MSH2, MSH3 and MSH6 were highly expressed in iPSCs compared wi

45 MutS that function in these processes, Msh2, Msh3 and Msh6, are involved in the mismatch repair of mu

46 Here we report that MSH3 and MSH6, but not MSH2, contain N-terminal sequence

47 MSH2 and preventing it from interacting with MSH3 and MSH6.

48 urification of Saccharomyces cerevisiae Msh2-Msh3 and performed a comparative study of Msh2-Msh3 and

49 Promoter methylation in MLH1, MLH3, MSH3 and PMS2 was also found to be significantly associa

50 ered mechanism of TGR in the absence of Msh2:Msh3 and Rad1 reveals a separate role for these proteins

51 possessed the mispair-binding specificity of Msh3 and revealed that communication between the MBD and

52 rovide a single, isogenic system to add back Msh3 and test key biochemical features of MutSbeta on ex

53 in knockout mice provide evidence that MSH2-MSH3 and the BER machinery promote trinucleotide repeat

54 clones, whereas mutations were dispersed in Msh3(-/-) and wild-type clones.

55 known cancer genes (ACVR2A, RNF43, JAK1, and MSH3) and three in genes not previously implicated as ca

56 NA junction that traps nucleotide-bound MSH2/MSH3, and inhibits its dissociation from the DNA.

57 h1 segregation data with that of pms1, msh2, msh3, and msh6 mutants show that the ability to promote

58 our data suggest that MutS homologues Msh2, Msh3, and Msh6 play overlapping and distinct roles durin

59 The mismatch repair enzymes MSH2, MSH3, and MSH6, implicated in repeat instability in othe

60 ree genes involved in mismatch repair--MSH2, MSH3, and MSH6--and one in nucleotide excision repair, R

61 es homologous to Escherichia coli mutS-MSH2, MSH3, and MSH6-function in MMR by recognizing mispaired

62 ously identified human MutS homologues MSH2, MSH3, and MSH6-genes that are involved in the pathogenes

63 ly similar to eukaryotic MutS homologs-MSH2, MSH3, and MSH6.

64 rt substrates requires the products of MSH2, MSH3, and RAD1 and that these proteins have functions in

65 1 interacts physically with Rad1/Rad10, Msh2/Msh3, and Rad52 proteins, and cells lacking SLX4 or SAW1

66 etic data on the mispair specificity of Msh2-Msh3- and Msh2-Msh6-dependent mismatch repair in vivo.

67 Therefore, we sequenced V and S regions from Msh3- and Msh6-deficient mice and compared mutations to

68 When the Msh3-/- and Msh6-/- mutations are combined, the tumor pr

69 cific DNA binding activity while domain I of MSH3 appeared important for mismatch binding specificity

70 tion of small insertion/deletion mispairs by Msh3 appears to require a greater degree of interactions

71 Five key lysine residues in Msh3 are direct targets of HDAC3 deacetylation.

72 s but not the mispair binding domain of Msh2-Msh3 are responsible for the extremely rapid dissociatio

73 MutSalpha (MSH2/MSH6) and MutSbeta (MSH2/MSH3) are eukaryotic mismatch recognition proteins that

74 -XPF), and the mismatch repair complex, Msh2-Msh3, are required for Z-DNA-induced genetic instability

75 amilies, MSH2, MSH6, MLH1, and PMS2, but not MSH3, are responsible for hereditary non-polyposis color

76 icantly from lymphoma to sarcoma, indicating MSH3 as a potent modulator of p53-driven tumorigenesis.

77 methylation was seen in MLH1, PMS2, MLH3 and MSH3 as well as significant heterogeneity for both MSI a

78 odimers AtMSH2*MSH6 (AtMutSalpha) and AtMSH2*MSH3 (AtMutSbeta) were previously found to bind the same

79 expansions as Msh3-/- cells, indicating that Msh3 ATPase function is critical for expansions.

80 he abundance of MutSbeta and rely heavily on Msh3 ATPase function.

81 Both ERCC1-XPF and MSH2-MSH3 bind to Z-DNA-forming sequences, though ERCC1-XPF r

82 homogeneity, and examined its effect on MSH2-MSH3 binding to DNA mismatches.

83 Therefore, MSH2-MSH3 binding to its substrates creates a unique nucleopr

84 t that the mismatch repair (MMR) factor MSH2-MSH3 binds and stabilizes branched recombination interme

85 In both pathways, Msh2-Msh3 binds double-strand/single-strand junctions and ini

86 and small insertion/deletion loops, and Msh2-Msh3 binds larger insertion/deletion loops.

87 MSH2/MSH3 binds, bends, and dissociates from repair-competent

88 function or polymorphic variants of Msh2 and Msh3, but in disparate experimental systems.

89 annealing also requires Rad1/Rad10 and Msh2/Msh3, but reveals a difference in their roles.

90 tations in the mismatch repair genes MSH2 or MSH3, but unaffected by a mutation in the nucleotide exc

91 Mutations in MSH6 or MSH3 cause partial defects in MMR, with inactivation of

92 Msh3-/- cells are severely defective for CTG*CAG repeat

93 Msh3-/- cells provide a single, isogenic system to add b

94 mal levels was as defective in expansions as Msh3-/- cells, indicating that Msh3 ATPase function is c

95 Analysis of an Msh2-Msh6/Msh3 chimeric protein and mutant Msh2-Msh3 complexes sho

96 nation of Cr-treated cells revealed MSH6 and MSH3 chromatin foci that originated in late S phase and

97 the Rad1/Rad10 complex, Saw1, Slx4, and Msh2/Msh3 complex at a 3' tailed recombination intermediate.

98 Our results show that the MSH2-MSH3 complex is important for the suppression of late-on

99 at the mismatch repair factor MutSbeta (Msh2-Msh3 complex) and the histone deacetylase HDAC3 function

100 the MSH2-MSH6 heterodimer, but not the MSH2-MSH3 complex, is responsible for modulating Ig hypermuta

101 ing a modulating role for the MutSbeta (MSH2-MSH3) complex in late-onset tumorigenesis.

102 2-Msh6/Msh3 chimeric protein and mutant Msh2-Msh3 complexes showed that the nucleotide binding domain

103 ons and CSR was greatly reduced, making Msh2/Msh3 contributions unlikely.

104 These results suggest that MSH3 cooperates with MSH6 in tumor suppression.

105 es to arsenate-resistant proteins, including MSH3, COX10, GCSH, PPOX, and MTHFD1, were also identifie

106 In mice, ablation of Msh2 or Msh6, but not Msh3, decreases levels of switch recombination and dimin

107 gether, our results support the concept that MSH3 deficiency causes EMAST or EMAST with low levels of

108 ely, our results provide novel evidence that MSH3 deficiency contributes to the cytotoxicity of plati

109 However, when Msh3 deficiency is combined with Msh6 deficiency (Msh3(-

110 this study, we first examined the effects of MSH3 deficiency on cytotoxicity caused by cisplatin and

111 sion in a Tet-off system, we discovered that MSH3 deficiency sensitized cells to both cisplatin and o

112 e prediction and treatments for cancers with MSH3 deficiency.

113 In contrast, Msh3-deficient Apc1638N mice showed no difference in sur

114 Msh3-deficient cells displayed a modest (16-fold) elevat

115 rt that MutS homologue 3 (MSH3) knockdown or MSH3-deficient cells exhibit the EMAST phenotype and low

116 Furthermore, MSH3-deficient cells maintained higher levels of phospho

117 3 was further supported by our findings that MSH3-deficient cells were sensitive to olaparib, a poly(

118 ine kinase 1 (HSV-tk1) gene was unchanged in Msh3-deficient ES cell lines but markedly elevated in Ms

119 reduced heavy chain class switching, whereas Msh3-deficient mice had normal antibody responses.

120 at cadmium inhibits both Msh2-Msh6- and Msh2-Msh3-dependent human MMR activity in vitro.

121 specific insertion/deletion mispairs by the MSH3-dependent mismatch repair pathway uses a heterodime

122 nferred a defect in both MSH2-MSH6- and MSH2-MSH3-dependent mismatch repair pathways.

123 egulation of the MLH1 protein did not affect MSH3-dependent toxicity of these drugs, indicating that

124 mutation alleles of Saccharomyces cerevisiae msh3 designed to disrupt mispair recognition fell into t

125 initiation became suppressed from within the Msh3, DHFR, and 2BE2121 transcription units.

126 (-10)) on chromosome 5 spanning three genes: MSH3, DHFR, and MTRNR2L2.

127 d within a polymorphic 9 bp tandem repeat in MSH3/DHFR, as the variant most significantly associated

128 MSH2-MSH3 directs the repair of insertion/deletion loops of u

129 that the mismatch recognition complex, MSH2/MSH3, discriminates between a repair-competent and a rep

130 hereas the hom3-10 reversion rate in an mlh3 msh3 double mutant was the same as in the respective sin

131 tide repeat, whereas Msh2-deficient and Msh2 Msh3 double-mutant cells displayed markedly increased le

132 to be mutated in vivo demonstrated that Msh2-Msh3 exhibited robust binding to specific base-base misp

133 the mispair, a mixture of Msh2-Msh6 (or Msh2-Msh3), Exo1, RPA, RFC-Delta1N, PCNA, and Pol epsilon was

134 A mixture of Msh2-Msh6 (or Msh2-Msh3), Exo1, RPA, RFC-Delta1N, PCNA, and Pol epsilon was

135 These results suggest that variation in the MSH3 exon 1 repeat region influences somatic expansion a

136 hich corresponds to a three-repeat allele in MSH3 exon 1 that is associated with a reduced rate of so

137 ed MMR reaction requiring Msh2-Msh6 (or Msh2-Msh3), exonuclease 1 (Exo1), replication protein A (RPA)

138 t, with both being required for IL-6-induced MSH3 export.

139 An ATPase-defective Msh3 expressed at normal levels was as defective in expa

140 sing isogenic HCT116-derived clones in which MSH3 expression is controlled by shRNA expression in a T

141 (EMAST) show reduced nuclear MutS homolog 3 (MSH3) expression with surrounding inflammation and porte

142 etion of SGS1, suggesting that Rad1 and Msh2:Msh3 facilitate TGR while Sgs1 opposes it.

143 The chromosomal double mutant msh3-FF>AA msh6-FF>AA eliminating the conserved FF resid

144 Formation of MSH3 foci was MSH6 and MLH1 dependent, whereas MSH6 foci

145 Msh2-Msh3 formed sliding clamps and recruited Mlh1-Pms1 on +1

146 show that the mismatch repair genes MSH2 and MSH3 function in mitotic recombination.

147 h2Delta1 mutants show strong defects in Msh2-Msh3 functions.

148 The MSH3 gene is one of the DNA mismatch repair (MMR) genes

149 role in mismatch repair (MMR), the MSH2 and MSH3 gene products are required to remove 3' nonhomologo

150 spans the dihydrofolate reductase (DHFR) and MSH3 genes.

151 tutions in the PCNA binding motif of Msh6 or Msh3 had elevated mutation rates, indicating that these

152 The mismatch repair gene MSH3 has been implicated as a genetic modifier of the CA

153 Accordingly, MSH3 has been suggested as a therapeutic target for CAG.

154 en the annealing partners are 1,170 bp, Msh2/Msh3 have little effect, while Rad1/Rad10 are still requ

155 ecific N-terminal regions (NTRs) of Msh6 and Msh3 have not been characterized other than by demonstra

156 e a previously unidentified role of the Msh2-Msh3 heterodimer in the recognition of base-base mispair

157 The Msh2-Msh3 heterodimer recognizes various DNA mispairs, includ

158 e mismatch recognition factor MutSbeta (MSH2-MSH3 heterodimer).

159 f the mismatch repair protein MutSbeta (Msh2-Msh3 heterodimer).

160 n of insertion/deletion mispairs by the Msh2-Msh3 heterodimer.

161 A human MSH2-human MSH3 (hMSH2.hMSH3) complex of approximately 1:1 stoichio

162 Msh2-Msh3 hops over nucleosomes and other protein roadblocks,

163 to the mismatch binding specificity of MSH2-MSH3 in genetic and biochemical assays.

164 However, the precise role of MSH3 in mediating the cytotoxic effects of ICL-inducing

165 ining illustrated a complete loss of nuclear MSH3 in normal and tumor tissue, confirming the LoF effe

166 To better study the role of MSH3 in tumor progression, we crossed Msh3(-/-) mice ont

167 In cells expressing Msh3 in which these lysine residues are mutated to argin

168 cumulation in the cytoplasm; reduced nuclear MSH3 increases EMAST and DNA damage.

169 the DNA mismatch repair genes pms1, msh2 and msh3, indicating that this effect does not require a fun

170 Ectopic expression of MSH2 and MSH3 induced GAA.TTC repeat expansion in the native FXN

171 no acid residues predicted to stabilize Msh2-Msh3 interactions with bent, strand-separated mispair-co

172 Msh2-Msh3 is also required for 3' non-homologous tail removal

173 anneal are 205 bp, the requirement for Msh2/Msh3 is as great as for Rad1/Rad10; but when the anneali

174 , suggesting that NLS1 function in Delta27bp MSH3 is compromised.

175 ue (Msh)6 (in conjunction with Msh2) but not Msh3 is involved in generating A/T base substitutions in

176 The absence or reduction of MSH3 is not strongly associated with cancer predispositi

177 clude that germ-line involvement of MSH6 and MSH3 is rare and that other genes are likely to account

178 molecular crosstalk mechanism, in which MSH2-MSH3 is used as a component of the BER machinery to caus

179 MutSbeta, a heterodimer of MSH2 and MSH3, is known to have a role in CAG.CTG repeat expansio

180 Here, we report that MutS homologue 3 (MSH3) knockdown or MSH3-deficient cells exhibit the EMAS

181 Because Msh3 lacks these conserved residues, we constructed a se

182 oss of the DNA mismatch repair (MMR) protein MSH3 leads to the development of a variety of tumors in

183 -null HCT116 cells activated an alternative, MSH3-like activity that restored dinucleotide repeat sta

184 an Msh2 MBD deletion mutant, indicating that Msh3-like behaviors beyond mispair specificity are not f

185 e stress, MSH3 with this deletion (Delta27bp MSH3) localizes to the cytoplasm, suggesting that NLS1 f

186 ate on a crowded genome and suggest how Msh2-Msh3 locates DNA lesions outside of replication-coupled

187 Our results suggest that MSH3 may also serve as a therapeutic target to slow the

188 tokine interleukin-6 (IL-6), suggesting that MSH3 may be a shuttling protein.

189 ing of the two classes of mutations onto the Msh3 MBD model appears to distinguish mispair recognitio

190 ertion/deletion loops is carried out by Msh2-Msh3-mediated mismatch repair (MMR).

191 se strains were completely defective in MSH2-MSH3-mediated MMR and recombination functions.

192 e binding pocket that are essential for Msh2-Msh3-mediated MMR but are largely dispensable for 3' NHT

193 MutSbeta (MSH2-MSH3) mediates repair of insertion-deletion heterologies

194 )(/)(-) mice have a decrease in CSR, whereas Msh3(-)(/)(-) mice do not.

195 Although none of these changes were seen in Msh3(-)(/)(-) mice, they had a higher percentage of larg

196 In contrast, Msh3(-)/- mice show no differences from their littermate

197 ole of MSH3 in tumor progression, we crossed Msh3(-/-) mice onto a tumor predisposing p53-deficient b

198 Cells from Msh3-/- mice are defective in repair of insertion/ delet

199 Msh3-/- mice develop tumors at a late age.

200 th MSH2-MSH3 and is decreased in Msh2-/- and Msh3-/- mice, suggesting a novel role for the MMR family

201 t interfere with both the Msh2-Msh6 and Msh2-Msh3 mismatch recognition complexes.

202 endonucleases and also associates with MSH2/MSH3 mismatch repair complex, telomere binding complex T

203 id BY4741, has an additional mutation in the MSH3 mismatch repair gene.

204 mbination was not altered by pms1, msh2, and msh3 mismatch repair mutations.

205 MSH2 that act as if they inactivate the Msh2-Msh3 mispair recognition complex thus causing weak MMR d

206 nitiated by either the Msh2-Msh6 or the Msh2-Msh3 mispair recognition heterodimer.

207 ndent of the mismatch correction genes MSH2, MSH3, MLH1, and PMS1, as judged by activity in mutant ex

208 ns in the yeast mismatch repair genes, MSH2, MSH3, MLH1, and PMS1.

209 Interestingly, Msh3(-/-) mouse embryonic fibroblasts displayed increase

210 but markedly elevated in Msh2-deficient and Msh3 Msh2 double-mutant cells.

211 ) cell lines homozygous for mutations at the Msh3, Msh2, and both Msh3 and Msh2 loci (2).

212 MSH2 and RAD10 were found to interact in msh3 msh6 and mlh1 pms1 double mutants, suggesting a dir

213 ve mismatch repair system (msh2, msh3, msh6, msh3 msh6, pms1, and mih1 mutants).

214 In Msh6(-)/- and Msh3(-)/-/Msh6(-)/- mice, base substitutions are prefere

215 tinal tumors from both Msh6(-/-)Apc1638N and Msh3(-/-)Msh6(-/-)Apc1638N mice contained truncation mut

216 However, in Msh3(-/-)Msh6(-/-)Apc1638N tumors, we observed a mixture

217 deficiency is combined with Msh6 deficiency (Msh3(-/-)Msh6(-/-)Apc1638N), the survival rate of the mi

218 sis by generating Apc1638N mice deficient in Msh3, Msh6 or both.

219 tor mutations were identified in MLH1, MSH2, MSH3, MSH6, and EXO1.

220 n Saccharomyces cerevisiae, the MMR proteins Msh3, Msh6, and Mlh1 interact with proliferating cell nu

221 epeats in the TGFbetaIIR, IGFIIR, BAX, E2F4, MSH3, MSH6, BRCA1, and BRCA2 genes were generally rare.

222 inactivation of MMR genes (MLH1, MLH2, MSH2, MSH3, MSH6, but not PMS1) in isogenic strains of Sacchar

223 ectly with several MMR components, including MSH3, MSH6, MLH1, and EXO1.

224 ostreplicative mismatch repair system (msh2, msh3, msh6, msh3 msh6, pms1, and mih1 mutants).

225 air changes from GC to CG and from AT to TA; msh3 mutants also accumulated homology-mediated duplicat

226 Saccharomyces cerevisiae msh3 mutants did not show an increase in the rate of bas

227 spectrum of mlh3 mutants paralleled that of msh3 mutants, suggesting that the Mlh1-Mlh3 heterodimer

228 The impact of the MSH3 mutations (c.1148delA, c.2319-1G>A, c.2760delC, and

229 The msh2 and msh3 mutations destabilized microsatellites with repeat

230 sent study, we identified biallelic germline MSH3 mutations in individuals with a suspected hereditar

231 The pedigrees, genotypes, and frequency of MSH3 mutations in the general population are consistent

232 Our data suggest that MSH3 mutations represent an additional recessive subtype

233 e initial recognition of Cr-DNA damage, MSH2-MSH3 (MutSbeta) complex was essential for the induction

234 It forms the MSH2-MSH6 (MutSalpha) and MSH2-MSH3 (MutSbeta) heterodimers, which help to ensure genom

235 the tissues exhibiting EMAST contained more MSH3-negative cells (average, 31.5%) than did the tissue

236 Although non-MSI-H CRC tissues contained MSH3-negative tumor cells ranging from 2% to 50% of the

237 Remarkably, MSH2-MSH3 not only stimulates pol beta to copy through the re

238 sidues within the FLY motif of the predicted Msh3 nucleotide binding pocket that are essential for Ms

239 Interestingly, chromosome 3 transfer into MSH3-null HCT116 cells activated an alternative, MSH3-li

240 nd governs whether a loop is removed by MSH2/MSH3 or escapes to become a precursor for mutation.

241 MutS homologues specific to either MMR (MSH2-MSH3 or MSH2-MSH6) or crossing over (MSH4-MSH5).

242 Interestingly, although mutations in either MSH3 or MSH6 do not cause the extreme microsatellite ins

243 When human MSH3 or MSH6 peptides containing the PCNA binding motif

244 SH2 functions in mismatch repair with either MSH3 or MSH6, and the MSH2-MSH3 and MSH2-MSH6 heterodime

245 is always found as a heterodimer with either Msh3 or Msh6, so it is important to know which one is in

246 d heterodimers of MSH2 complexed with either MSH3 or MSH6.

247 ase Exo1, and mismatch repair mutants (msh2, msh3, or msh6).

248 isruptions of the mismatch repair gene MSH2, MSH3, or PMS1 or the recombination gene RAD52 showed lit

249 s severely inhibited in the absence of MSH2, MSH3, or RAD1 and is relatively insensitive to the prese

250 parent absence of a Saccharomyces cerevisiae MSH3 ortholog in the C. elegans genome, suggests that C.

251 Msh3 overexpression led to high expansion activity and e

252 Deacetylation sites in Msh3 overlap a nuclear localization signal, and we show

253 ere associated with progression in TRACK-HD (MSH3 p=2.94 x 10(-8)DHFR p=8.37 x 10(-7) MTRNR2L2 p=2.15

254 10(-9)) and to a lesser extent in REGISTRY (MSH3 p=9.36 x 10(-4)DHFR p=8.45 x 10(-4)MTRNR2L2 p=1.20

255 Survival of Msh3/p53 mice was not reduced compared with p53 single m

256 Msh3/p53 tumors showed increased loss of heterozygosity,

257 by residues ((L/I)SRFF) embedded within the MSH3 PCNA-binding motif.

258 rate DNA, with or without Msh2-Msh6 (or Msh2-Msh3), PCNA, and RFC but did not require nicking of the

259 with MSH3-proficient cells, suggesting that MSH3 plays an important role in repairing DNA double str

260 mutations were obtained in MLH1, PMS1, MSH2, MSH3, POL30 (PCNA), POL32, and RNR1, whereas starting wi

261 Expression of two Msh3 polymorphic variants at normal levels showed no det

262 ter oxaliplatin treatment in comparison with MSH3-proficient cells, suggesting that MSH3 plays an imp

263 vation reaction requiring Msh2-Msh6 (or Msh2-Msh3), proliferating cell nuclear antigen (PCNA), and re

264 gesting these polymorphisms primarily affect Msh3 protein stability, not activity.

265 A msh3 rad59 double mutant was more severely defective in

266 We suggest Msh2 and Msh3 recognize not only heteroduplex loops and mismatche

267 c MutS homolog complexes, Msh2-Msh6 and Msh2-Msh3, recognize mismatched bases in DNA during mismatch

268 Knockout of Msh3 reduces somatic expansion in Huntington's disease m

269 all insertion/deletion mismatches while MSH2-MSH3 repairs larger insertion/deletion mismatches.

270 tes of frameshift mutations; inactivation of MSH3 results in low rates of frameshift mutations.

271 MSH3 reversibly exits from the nucleus to the cytosol in

272 that in the absence of MSH2 or MSH6, but not MSH3, reversion rates of some mutations are increased by

273 Overall, MSH3's shuttling in response to inflammation enables acc

274 for the extremely rapid dissociation of Msh2-Msh3 sliding clamps from DNA relative to that seen for M

275 show that shRNA knockdown of either MSH2 or MSH3 slowed GAA.TTC expansion in our system.

276 Remarkably, the Msh3-specific mispair-binding domain (MBD) licences a ch

277 cal footprinting analyses indicate that MSH2-MSH3 specifically binds at the double-strand/single-stra

278 mobility shift assay that S. cerevisiae MSH2-MSH3 specifically binds branched DNA substrates containi

279 endent, whereas MSH6 foci were unaffected by MSH3 status.

280 showed that it is a metal-dependent and Msh2-Msh3-stimulated endonuclease that makes single-strand br

281 homolog 6 (Msh6) or the Msh2-MutS homolog 3 (Msh3) stimulates 5' to 3' excision by exonuclease 1 (Exo

282 osatellite alterations in the pms1, msh2 and msh3 strains were additions or deletions of single GT re

283 Further, they demonstrate that MSH2-MSH3 suppresses chromosomal instability and modulates th

284 ed with Msh2/p53 tumors, revealing that MSH2-MSH3 suppresses tumorigenesis by maintaining chromosomal

285 vivo analysis of well-conserved residues in Msh3 that are hypothesized to be required for MMR and/or

286 Here, we show that MSH3, the MSH2-binding partner in the MutSbeta complex,

287 It interacts with MSH6 or MSH3 to form the MutSalpha or MutSbeta complex, respecti

288 matches and suggest that the binding of MSH2-MSH3 to mismatch DNA involves protein-DNA contacts that

289 otide insertion/deletion mismatches and with MSH3 to recognize small loop insertion/deletion mismatch

290 MSH3, together with MSH2, forms the MutSbeta heteroduple

291 endonuclease Rad1/Rad10 but also on Msh2 and Msh3, two proteins that are required to correct mismatch

292 eling of the mispair-binding domain (MBD) of Msh3 using the related Msh6 MBD revealed that mismatch r

293 sh6 was replaced by the equivalent domain of Msh3 was functional for mismatch repair.

294 This role of MSH3 was further supported by our findings that MSH3-def

295 Here, human Msh3 was mutated to selectively inactivate MutSbeta.

296 Whereas MSH3 was not involved in any family, a large Amsterdam-p

297 no FEN1 mutations, a frameshift mutation in MSH3 was observed in an endometrial carcinoma and in an

298 In strains deleted of RAD1, MSH2, or MSH3, we find that the frequency of TGR is reduced and t

299 To examine the role of MSH3, we generated a mouse with a null mutation in this

300 MSH2 and MSH3, which encode subunits of Msh2/3, a complex active

301 With oxidative stress, MSH3 with this deletion (Delta27bp MSH3) localizes to th