ライフサイエンスコーパス: MSH2

1 ance (VUS), focusing on mutator S homolog 2 (MSH2).

2 in mutL homolog 1 (MLH1) and mutS homolog 2 (MSH2).

3 spective set of 48 VUS (25 in MLH1 and 23 in MSH2).

4 riants in the key DNA mismatch repair factor MSH2.

5 ypes can be rescued by ectopic expression of MSH2.

6 in an UNG-dependent manner but are offset by MSH2.

7 ase 10 (USP10) interacts with and stabilizes MSH2.

8 trolling the DNA mismatch repair function of MSH2.

9 and histone deacetylase (HDAC6) deacetylates MSH2.

10 of the upstream mismatch recognition factor MSH2.

11 match repair activities by downregulation of MSH2.

12 s BIR/RMD in a manner partially dependent on MSH2.

13 mainly as a result of mutations in MLH1 and MSH2.

14 se mutation in the mismatch repair component MSH2.

15 chanisms of somatic inactivation of MLH1 and MSH2.

16 ), BRCA2 (5.8%), CHEK2 (1.4%), BRIP1 (0.9%), MSH2 (0.8%), and ATM (0.6%).

17 ATM, 1 in BRCA1, 2 in BRCA2, 1 in MLH1, 2 in MSH2, 1 in MSH6, and 1 in TP53.

18 e with constitutional MLH1 methylation]; 16, MSH2; 1, MSH2/monoallelic MUTYH; 2, MSH6; 5, PMS2); 1 pa

19 he MMR gene product: 31 in MLH1 (61%), 11 in MSH2 (21%), 3 in MSH6 (6%), and 6 in PMS2 (12%); 8 mutat

20 ed with Lynch syndrome (25 with mutations in MSH2, 24 with mutations in MLH1, 5 with mutations in MSH

21 ency was most commonly due to alterations in MSH2 (53%) or MSH6 (23%).

22 Loss of MutS homolog 2 (MSH2), a mismatch repair (MMR) protein, abrogated early

23 ly unrecognized consequence of deficiency in MSH2, a protein known primarily for its function in corr

24 Deleterious mutations in human MSH2 account for approximately half of the alleles assoc

25 t simultaneous deficiency of UNG and MSH2 or MSH2 alone causes genomic instability and a shorter late

26 unohistochemical analyses were performed for MSH2, along with allele-specific PCR assays.

27 polymerase kappa (Polkappa) can partner with MSH2, an important mismatch repair protein associated wi

28 2dC significantly restored the expression of MSH2 and doxorubicin-induced cytotoxicity in Caki-1 cell

29 o resolve the ~1,300 extant missense VUSs in MSH2 and may facilitate the prospective classification o

30 g of uracil lesions (likely U/G mispairs) by MSH2 and MLH1 (likely noncanonical MMR).

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

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

33 ease in the mismatch repair (MMR) components MSH2 and MSH6 have profound effects on temozolomide sens

34 RNAi-mediated attenuation of MSH2 and MSH6 showed that such modest decreases provided

35 ss of staining for the mismatch repair genes MSH2 and MSH6.

36 tumor samples, which was most pronounced for MSH2 and MSH6.

37 get genes in the combined absence of UNG and MSH2 and that DNA strand lesions arise in an UNG-depende

38 Patients with MSI and loss of MSH2 and/or MSH6 expression, isolated loss of PMS2 or lo

39 ly classified variants (19 in MLH1 and 21 in MSH2) and a prospective set of 48 VUS (25 in MLH1 and 23

40 g similar to that found in MutS homologue 2 (Msh2)- and Mlh1-deficient B cells.

41 tions in MLH1, 29 patients with mutations in MSH2, and 3 with mutations in MSH6) for somatic mutation

42 downstream targets IKBKB, WEE1, FGF2, RAD50, MSH2, and KIT.

43 were identified based on detection of MLH1, MSH2, and MSH6 proteins and methylation of the MLH1 prom

44 ates that this HWA is able to classify MLH1, MSH2, and MSH6 VUSs as either benign or pathogenic with

45 Mutations in mismatch repair genes (EXO1, MSH2, and MSH6) were associated with microsatellite inst

46 ons in the mismatch repair (MMR) genes MLH1, MSH2, and MSH6.

47 in three mismatch repair (MMR) genes: MLH1, MSH2, and MSH6.

48 Abnormal IHC results, including absence of MSH2, are not diagnostic of LS and should be interpreted

49 HDAC10 is the major enzyme that deacetylates MSH2 at Lys-73.

50 ion, and disruption of the MutS homologue 2 (MSH2)-ATR module.

51 ur results highlight the powerful effects of MSH2 attenuation as a potent mediator of temozolomide re

52 Here, we show that MSH3, the MSH2-binding partner in the MutSbeta complex, is require

53 sis catalog for the MMR gene MutS Homolog 2 (Msh2) by mutagenizing, identifying, and cataloging 26 de

54 However, whether other regions of MSH2 can be acetylated and whether other histone deacety

55 Here, we report that MSH2 can be acetylated at Lys-73 near the N terminus.

56 We created mice in which the MMR gene Msh2 can be inactivated in a defined fraction of crypt b

57 Moreover, we observed that MSH2 can facilitate TLS across cyclobutane pyrimidine di

58 in PCNA monoubiquitination, indicating that MSH2 can regulate post-UV focus formation by specialized

59 able to assess whether variants in MLH1 and MSH2 cause defects in DNA MMR.

60 Mutation or dysregulation of MSH2 causes genomic instability that can lead to cancer.

61 vity, because DeltaAID is not a DN mutant in msh2(-/-) cells.

62 Ung(-/-), Msh2(-/-), Msh6(-/-), and Ung(-/-) Msh2(-/-) clones suggest that pol zeta may function in t

63 A biosensor based on mSH2 closely reported the kinetics of EGFR phosphorylati

64 as butyrate that fuel hyperproliferation of MSH2(-/-) colon epithelial cells.

65 enes, 17 of which, including TCF7L2, TWIST2, MSH2, DCC, EPHB1 and EPHB2 have been previously implicat

66 ne acetyltransferases (HATs) are involved in MSH2 deacetylation/acetylation is unknown.

67 In addition, knockdown of MSH2 decreases the cellular mismatch repair activity.

68 We anticipate that identifying MSH2 defects in infecting strains may influence the mana

69 We documented that Msh2 deficiency causes dysmyelination of the axonal proj

70 ngs reveal a novel pathogenic consequence of MSH2 deficiency, providing a new mechanistic hint to pre

71 arcinomas than control mice; all tumors were MSH2 deficient.

72 We traced the fate of MSH2-deficient crypts under the influence of different e

73 in mutation per mitosis rate was observed in Msh2-deficient epithelium (2.4 x 10(-2)) compared to wil

74 crosatellite mutation rates in wild-type and Msh2-deficient epithelium were established.

75 f crypt base columnar stem cells to generate MSH2-deficient intestinal crypts among an excess of wild

76 to the methylating agent temozolomide caused MSH2-deficient intestinal stem cells to proliferate more

77 The MSH2-deficient intestinal stem cells were able to coloni

78 In 13 of 25 tumors (8 MLH1-deficient and 5 MSH2-deficient tumors), we identified 2 somatic mutation

79 cetylates and ubiquitinates MSH2, leading to MSH2 degradation.

80 Null mutations in UNG and MSH2 demonstrate the complementary roles of the base exc

81 Thus, we propose that regulation of MSH2-dependent DNA damage response underlies the importa

82 inal binding protein interacting protein and MSH2-dependent DSB repair during CSR.

83 terminal binding protein interacting protein/MSH2-dependent pathway that relies on microhomology can

84 Surprisingly, MSH2-dependent recombination suppression was not evident

85 MSH2 depletion also suppresses ICL sensitivity in cells

86 MSH2 depletion suppresses an aberrant DNA damage respons

87 Therefore, the level of MSH2 determines DNA damage response.

88 patients with pathogenic variants in MLH1 or MSH2 developed CRC in 10 years (11.3% and 11.4%) than pa

89 Loss of MSH2 did not correlate with age.

90 ants interacted with San1, whereas wild-type Msh2 did not.

91 ologous 3' tail, the mismatch repair protein Msh2 does not discourage homeologous recombination.

92 carrying alterations in mismatch repair gene MSH2 exhibit a higher propensity to breakthrough antifun

93 e of DNA hypermethylation in inactivation of MSH2 expression and consequently MMR-dependent apoptosis

94 Lgr5-CreERT2;Msh2(flox/-) mice developed more adenomas and adenocarci

95 Exposure of Lgr5-CreERT2;Msh2(flox/-) mice to the methylating agent temozolomide

96 mouse model of Lynch syndrome (Lgr5-CreERT2;Msh2(flox/-) mice) and found that environmental factors

97 an excess of wild-type crypts (Lgr5-CreERT2;Msh2(flox/-) mice).

98 sessing the pathogenicity of VUS in MLH1 and MSH2 found in patients with suspected Lynch syndrome.

99 Loss or depletion of MSH2 from cells renders resistance to certain DNA-damagi

100 t interaction with MLH1, and the MMR protein MSH2 function in a common pathway in response to UV irra

101 Msh2(G674A) or Msh6(T1217D) mice that have mutations in

102 Mutant human MutSalpha proteins MSH2(G674A)-MSH6(wt) and MSH2(wt)-MSH6(T1219D) are profi

103 de binding and mismatch recognition, whereas MSH2(G674A)-MSH6(wt) has a partial defect in nucleotide

104 VUS were introduced into the endogenous Msh2 gene of mouse embryonic stem cells by oligo targeti

105 ethod to test the effects of VUS in MLH1 and MSH2 genes found in patients with suspected Lynch syndro

106 repair and decreased expression of Mlh1 and Msh2 genes, defects frequently observed in human sebaceo

107 among individuals with mutations in MLH1 or MSH2 (hazard ratio, 13.9; 95% CI, 3.44-56.5).

108 h several Class I and II HDACs interact with MSH2, HDAC10 is the major enzyme that deacetylates MSH2

109 We found that depletion of MSH2 impairs PCNA monoubiquitination and the formation o

110 In addition, shRNA silencing of MSH2 impeded CTG.CAG triplet-repeat expansion.

111 sed expression of mismatch repair (MMR) gene MSH2 in cells exposed to oxidative stress suggests that

112 in living cells, presenting a novel role of MSH2 in post-UV cellular responses.

113 Interestingly, expression of MSH2 in Rad18-deficient cells increased UV-induced Polka

114 Our results reveal a pro-crossover role for MSH2 in regions of higher sequence diversity in A. thali

115 USP10 deubiquitinates MSH2 in vitro and in vivo Moreover, the protein level of

116 utL homologue 1 (MLH1) and MutS homologue 2 (MSH2) in HPCs and colony-forming cell-derived clones (CF

117 eroduplex DNA, and some provided evidence of MSH2-independent correction.

118 We show that MSH2 interacts with FEN1 and facilitates its nuclease ac

119 MSH2 is a key DNA mismatch repair protein, which plays a

120 MSH2 is acetylated at its C terminus, and histone deacet

121 ite its essential role in GAA.TTC expansion, MSH2 is not an attractive therapeutic target.

122 o and in vivo Moreover, the protein level of MSH2 is positively correlated with the USP10 protein lev

123 MSH2 is required for DNA mismatch repair recognition in

124 rated that the mismatch repair (MMR) protein MSH2 is required for expansions in a mouse model of thes

125 in S regions, and we find in this study that Msh2 is required for the DN activity, because DeltaAID i

126 MutS protein homolog 2 (MSH2) is a key DNA mismatch repair protein.

127 MutS homolog 2 (MSH2) is an essential DNA mismatch repair (MMR) protein.

128 s), DNA repair/replication processes (PARP1, MSH2, Ku, DNA-PKcs, MCM proteins, PCNA and DNA Pol delta

129 sequentially deacetylates and ubiquitinates MSH2, leading to MSH2 degradation.

130 t one variant, but did not elevate wild-type Msh2 levels.

131 Rescue by Msh2 loss was confirmed in Fancd2-null primary mouse cel

132 lase (UNG)-mediated base-excision repair and MSH2-mediated mismatch repair (MMR) to yield mutations a

133 pecific affinity maturation in AID(S38A/S38A)MSH2(-/-) mice is not significantly elevated in response

134 Observations in Ung(-/-) Msh2(-/-) mice suggest that many other genes efficiently

135 egulatory context, from 83 genes in Ung(-/-) Msh2(-/-) mice to identify common properties of AID targ

136 robiota composition reduces CRC in APC(Min/+)MSH2(-/-) mice, and that a diet reduced in carbohydrates

137 usly, we characterized clinically identified MSH2 missense mutations, using yeast as a model system,

138 lymerase-delta, although the repair proteins Msh2, Mlh1 and Exo1 influence the extent of correction.

139 ations were most frequent, followed by PMS2, MSH2, MLH1, and EPCAM mutations, respectively.

140 genes (BRCA1, BRCA2, BRIP1, RAD51C, RAD51D, MSH2, MLH1, PMS2, and MSH6) bring the total number of ge

141 ation of the DNA mismatch repair genes MLH1, MSH2, MLH3, MSH6, PMS2, MGMT and MLH3 via methylation sp

142 mplete loss of nuclear expression of MLH1 or MSH2 MMR gene products by immunohistochemistry (IHC).

143 nstitutional MLH1 methylation]; 16, MSH2; 1, MSH2/monoallelic MUTYH; 2, MSH6; 5, PMS2); 1 patient had

144 rve a complete block in CSR in AID(S38A/S38A)MSH2(-/-) mouse B cells that correlates with an impaired

145 egligible at the JH4 intron in AID(S38A/S38A)MSH2(-/-) mouse B cells, and, consistent with this, NP-s

146 The mismatch repair components MSH2, MSH3 and MSH6 were highly expressed in iPSCs compa

147 The mismatch repair enzymes MSH2, MSH3, and MSH6, implicated in repeat instability i

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

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

150 h2-Msh3 and performed a comparative study of Msh2-Msh3 and Msh2-Msh6 for mispair binding, sliding cla

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

152 and purification of Saccharomyces cerevisiae Msh2-Msh3 and performed a comparative study of Msh2-Msh3

153 udies in knockout mice provide evidence that MSH2-MSH3 and the BER machinery promote trinucleotide re

154 egions but not the mispair binding domain of Msh2-Msh3 are responsible for the extremely rapid dissoc

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

156 In both pathways, Msh2-Msh3 binds double-strand/single-strand junctions an

157 Our results show that the MSH2-MSH3 complex is important for the suppression of la

158 es that the mismatch repair factor MutSbeta (Msh2-Msh3 complex) and the histone deacetylase HDAC3 fun

159 n Msh2-Msh6/Msh3 chimeric protein and mutant Msh2-Msh3 complexes showed that the nucleotide binding d

160 Msh2-Msh3 formed sliding clamps and recruited Mlh1-Pms1

161 es the mismatch recognition factor MutSbeta (MSH2-MSH3 heterodimer).

162 ce, of the mismatch repair protein MutSbeta (Msh2-Msh3 heterodimer).

163 Msh2-Msh3 hops over nucleosomes and other protein roadbl

164 t amino acid residues predicted to stabilize Msh2-Msh3 interactions with bent, strand-separated mispa

165 Msh2-Msh3 is also required for 3' non-homologous tail re

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

167 navigate on a crowded genome and suggest how Msh2-Msh3 locates DNA lesions outside of replication-cou

168 is initiated by either the Msh2-Msh6 or the Msh2-Msh3 mispair recognition heterodimer.

169 Remarkably, MSH2-MSH3 not only stimulates pol beta to copy through t

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

171 Further, they demonstrate that MSH2-MSH3 suppresses chromosomal instability and modulat

172 ompared with Msh2/p53 tumors, revealing that MSH2-MSH3 suppresses tumorigenesis by maintaining chromo

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

174 ' to the mispair, a mixture of Msh2-Msh6 (or Msh2-Msh3), Exo1, RPA, RFC-Delta1N, PCNA, and Pol epsilo

175 A mixture of Msh2-Msh6 (or Msh2-Msh3), Exo1, RPA, RFC-Delta1N, PCNA, and Pol epsilo

176 irected MMR reaction requiring Msh2-Msh6 (or Msh2-Msh3), exonuclease 1 (Exo1), replication protein A

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

178 activation reaction requiring Msh2-Msh6 (or Msh2-Msh3), proliferating cell nuclear antigen (PCNA), a

179 cule fluorescence imaging to investigate how Msh2-Msh3, a eukaryotic mismatch repair complex, navigat

180 ERCC1-XPF), and the mismatch repair complex, Msh2-Msh3, are required for Z-DNA-induced genetic instab

181 h genetic data on the mispair specificity of Msh2-Msh3- and Msh2-Msh6-dependent mismatch repair in vi

182 f insertion/deletion loops is carried out by Msh2-Msh3-mediated mismatch repair (MMR).

183 eotide binding pocket that are essential for Msh2-Msh3-mediated MMR but are largely dispensable for 3

184 and showed that it is a metal-dependent and Msh2-Msh3-stimulated endonuclease that makes single-stra

185 CC1-XPF recruitment to Z-DNA is dependent on MSH2-MSH3.

186 or nucleotide binding and/or exchange within Msh2-Msh3.

187 y of the Rad1/Rad10 complex, Saw1, Slx4, and Msh2/Msh3 complex at a 3' tailed recombination intermedi

188 type, Polzeta(+/-), Polzeta(-/-), Ung(-/-), Msh2(-/-), Msh6(-/-), and Ung(-/-) Msh2(-/-) clones sugg

189 teins MutL homolog 1 (MLH1), MutS homolog 2 (MSH2), MSH6, and PMS1 homolog, mismatch repair system co

190 deleterious mutations in BRCA1, BRCA2, MLH1, MSH2, MSH6 and PMS2 to invasive epithelial ovarian cance

191 in the Lynch syndrome-associated genes MLH1, MSH2, MSH6 and PMS2.

192 g repression of the mismatch repair proteins MSH2, MSH6, and EXO1 as well as the homologous recombina

193 resence of 4 mismatch repair proteins (MLH1, MSH2, MSH6, and PMS2) in these tumors.

194 dy of AAs with mutations in MMR genes (MLH1, MSH2, MSH6, and PMS2) using databases from 13 US referra

195 ing the mismatch repair (MMR) proteins MLH1, MSH2, MSH6, and PMS2; when the second allele becomes mut

196 Mutated gene (MLH1, MSH2, MSH6, and/or PMS2) and type of mutation (truncatin

197 yses of tissue microarrays for loss of MLH1, MSH2, MSH6, and/or PMS2.

198 ed on loss of mismatch repair proteins MLH1, MSH2, MSH6, and/or PMS2.

199 he MutSalpha-MutLalpha complex consisting of Msh2, Msh6, Mlh1, and Pms1.

200 = 2), ATM (n = 2), and BRCA1, BRCA2, PALB2, MSH2, MSH6, NBN, FANCB, and PMS1 (n = 1 each).

201 d the expression of the DNA repair proteins, MSH2, MSH6, OGG1 and BRCA1.

202 ations in mismatch repair (MMR) genes (MLH1, MSH2, MSH6, or PMS2) develop a rare but severe variant o

203 crosatellite instability, namely MLH1, PMS2, MSH2, MSH6, P53 and PTEN.

204 ons in APC, ATM, BRCA1, BRCA2, CDKN2A, MLH1, MSH2, MSH6, PALB2, PMS2, PRSS1, STK11, and TP53 in patie

205 ATM, ATR, BRCA1, BRCA2, FANCA, FANCD2, MLH1, MSH2, MSH6, PALB2, POLD1, POLE, PRKDC, and RAD50) and ca

206 variants in the mismatch repair genes (MLH1, MSH2, MSH6, PMS2, EPCAM).

207 LS-associated mismatch repair genes ( MLH1, MSH2, MSH6, PMS2, EPCAM).

208 Tumor DNA was sequenced for MLH1, MSH2, MSH6, PMS2, EPCAM, POLE, and POLD1 with ColoSeq an

209 It forms the MSH2-MSH6 (MutSalpha) and MSH2-MSH3 (MutSbeta) heterodim

210 ained a nick 3' to the mispair, a mixture of Msh2-Msh6 (or Msh2-Msh3), Exo1, RPA, RFC-Delta1N, PCNA,

211 A mixture of Msh2-Msh6 (or Msh2-Msh3), Exo1, RPA, RFC-Delta1N, PCNA,

212 dent 3' nick-directed MMR reaction requiring Msh2-Msh6 (or Msh2-Msh3), exonuclease 1 (Exo1), replicat

213 lh1-Pms1 with substrate DNA, with or without Msh2-Msh6 (or Msh2-Msh3), PCNA, and RFC but did not requ

214 1 endonuclease activation reaction requiring Msh2-Msh6 (or Msh2-Msh3), proliferating cell nuclear ant

215 h the ability to form a ternary complex with Msh2-Msh6 and mismatch DNA.

216 or the mispair-dependent interaction between Msh2-Msh6 and Mlh1-Pms1.

217 eins had defects either in trimerization and Msh2-Msh6 binding or in activation of the Mlh1-Pms1 endo

218 air recognition and Mlh1-Pms1 recruitment by Msh2-Msh6 but not sliding clamp formation.

219 ven conformational change and resulted in an Msh2-Msh6 complex that bound mispaired bases but could n

220 rformed a comparative study of Msh2-Msh3 and Msh2-Msh6 for mispair binding, sliding clamp formation,

221 nd CC, AA, and possibly GG mispairs, whereas Msh2-Msh6 formed mispair-dependent sliding clamps and re

222 Supporting this hypothesis, Msh2-Msh6 have been shown to contribute to DSB formation

223 anced by an msh6 mutation that disrupted the Msh2-Msh6 interaction with PCNA.

224 xo1-independent MMR pathway and suggest that Msh2-Msh6 localizes PCNA to repair sites after mispair r

225 Delta, over-retained PCNA hyper-recruits the Msh2-Msh6 mismatch recognition complex through its PCNA-

226 ATP binding causes the mispair-bound Msh2-Msh6 mismatch recognition complex to slide along th

227 recognition protein could substitute for the Msh2-Msh6 mispair recognition protein and showed a diffe

228 Our studies contrast how Msh2-Msh3 and Msh2-Msh6 navigate on a crowded genome and suggest how M

229 In the other, Msh2-Msh6 or Msh2-Msh3 activate the MutL homolog 1 (Mlh1

230 A mismatch repair is initiated by either the Msh2-Msh6 or the Msh2-Msh3 mispair recognition heterodim

231 es suggest that pol zeta may function in the MSH2-MSH6 pathway.

232 In contrast, Msh2-Msh6 slides without hopping and is largely blocked

233 air-binding domain (MBD) licences a chimeric Msh2-Msh6(3MBD) to bypass nucleosomes.

234 glycosylase (UNG) or mutS homologs 2 and 6 (MSH2-MSH6) proteins, and then processed into DNA breaks.

235 ng clamps from DNA relative to that seen for Msh2-Msh6, and that amino acid residues predicted to sta

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

237 Analysis of an Msh2-Msh6/Msh3 chimeric protein and mutant Msh2-Msh3 com

238 s that ATP induces conformational changes in Msh2-Msh6; however, the nature of these conformational c

239 mans and mice make it unclear to what extent MSH2/MSH6 can complement for UNG in vivo.

240 cosylase (UNG) or the mismatch repair factor MSH2/MSH6, must process the deoxyuridine to initiate cla

241 Therefore, we mapped crossovers in a msh2 mutant, defective in mismatch recognition, using mu

242 gh total crossover numbers were unchanged in msh2 mutants, recombination was remodelled from the dive

243 regions in wild type Arabidopsis, but not in msh2 mutants.

244 ved by the mismatch correction deficiency of Msh2(-/-) mutants.

245 ding 10 MSH6 mutation carriers (0.45%) and 4 MSH2 mutation carriers (0.18%).

246 MSH2 mutation carriers had a considerably higher risk of

247 Among MSH2 mutation carriers, mutations in MSH2 (the most prev

248 2 mutations were more frequent than MLH1 and MSH2 mutations ( P = 2.3 x 10(-5)).

249 2 mutations were more frequent than MLH1 and MSH2 mutations among patients who met BRCA1/2 testing cr

250 ispair binding by either the MutS homolog 2 (Msh2)-MutS homolog 6 (Msh6) or the Msh2-MutS homolog 3 (

251 A mixture of MutS homolog 2 (Msh2)-MutS homolog 6, Exonuclease 1, replication protein

252 omolog 2 (Msh2)-MutS homolog 6 (Msh6) or the Msh2-MutS homolog 3 (Msh3) stimulates 5' to 3' excision

253 The Msh2-MutS homolog 3 mispair recognition protein could su

254 (30)); MSH2 (MutShomolog 2) and HSP60 (heat-shock protein 60)(2

255 t cohort; mutations included MLH1 (n = 306), MSH2 (n = 354), MSH6 (n = 177), PMS2 (n = 141), and EPCA

256 e-penetrance genes were BRCA2 (n = 9; 1.5%), MSH2 (n = 8; 1.4%), BRCA1 (n = 8; 1.4%), CHEK2 (n = 6; 1

257 8 MMR gene mutation carriers (MLH1, n = 806; MSH2, n = 1,004; MSH6, n = 308).

258 expressed MLH1 or MSH2 variants in MLH1- or MSH2-null human colorectal cancer cell lines (HCT116 or

259 Msh2-null mice were also impaired in locomotive activity

260 he myelinated corpus callosum projections of Msh2-null mice were smaller than wild-type mice, whereas

261 mutations in or near the ATP binding site of MSH2 or ATP hydrolysis catalytic site of MSH6 develop ca

262 rmline mutation in 1 allele of the MMR genes MSH2 or MLH1.

263 at later ages than carriers of mutations in MSH2 or MLH1.

264 show that simultaneous deficiency of UNG and MSH2 or MSH2 alone causes genomic instability and a shor

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

266 Mutations are frequently complex MSH2 or MSH6 structural rearrangements rather than MLH1

267 for mutation in TP53, RB1, BRCA2, PIK3CA, or MSH2, or expression of SOX2 or ERG and ARSi resistance.

268 h syndrome associated with variants in MLH1, MSH2, or MSH6 from Germany, the Netherlands, and Finland

269 tations in patients exhibiting loss of MSH6, MSH2, or PMS2 or loss of MLH1/PMS2 with absence of MLH1

270 ts with pathogenic variants in MLH1 vs 7% in MSH2 (P = .002).

271 atellite instability phenotype compared with Msh2/p53 tumors, revealing that MSH2-MSH3 suppresses tum

272 Overall, our results suggest a novel USP10-MSH2 pathway regulating DNA damage response and DNA mism

273 ns using four different markers (MLH1, MSH6, MSH2, PMS2).

274 MSH2 preferentially binds a cisplatin interstrand cross-

275 y are opposed by the protective influence of MSH2, producing a net protective effect that promotes im

276 tone H3 acetylation, and hypermethylation of MSH2 promoter were also observed in Caki-1 cells adapted

277 contains a 3' protruding nonhomologous tail, Msh2 promotes the rejection of mismatched substrates.

278 Immunostaining showed that MSH2 protein accumulates on meiotic chromosomes during p

279 Previous studies showed that the level of MSH2 protein is modulated by the ubiquitin-proteasome pa

280 ismatch repair was low levels of the variant Msh2 proteins.

281 ted Lynch syndrome carry variants in MLH1 or MSH2, proteins encoded by these genes are required for D

282 romosomes during prophase I, consistent with MSH2 regulating meiotic recombination.

283 the deubiquitinating enzymes, which regulate MSH2 remain unknown.

284 In addition to its DNA repair function, MSH2 serves as a sensor for DNA base analogs-provoked DN

285 iants of unknown significance in ATM, BRCA1, MSH2, SLX4, ERCC, and various FANC genes were detected.

286 Compared to tSH2-WT and mSH2, SPY992 exhibited superior performance as a specifi

287 Among MSH2 mutation carriers, mutations in MSH2 (the most prevalent mutations overall) were most co

288 zolomide-treated GBM patients, we found that MSH2 transcripts in primary GBM could predict patient re

289 ajor mechanism for increased turnover of the Msh2 variants and identified the primary ubiquitin ligas

290 We transiently expressed MLH1 or MSH2 variants in MLH1- or MSH2-null human colorectal can

291 rs from patients with pathogenic variants in MSH2 vs 11% in MLH1 (P = .015).

292 7.8% in patients with pathogenic variants in MSH2 vs 7.7% in MLH1 (P < .001).

293 6 (4.7%) (P = .001 and P = .003 for MLH1 and MSH2 vs MSH6, respectively).

294 polymorphisms and was used to investigate 59 Msh2 VUS.

295 the miR-21 tumor-related targets, including MSH2, was observed in Ras-transformed keratinocytes.

296 BRCA2 and MSH2 were significantly associated with an increased ris

297 nograft model of human GBM, small changes in MSH2 were sufficient to suppress temozolomide-induced tu

298 H2) of PLCgamma1 and isolated a mutant form (mSH2) with enhanced specificity for phosphorylated Tyr(9

299 MutSalpha proteins MSH2(G674A)-MSH6(wt) and MSH2(wt)-MSH6(T1219D) are profiled in a variety of funct

300 MSH2(wt)-MSH6(T1219D) fails to couple nucleotide binding