ライフサイエンスコーパス: PMS2

1 ng four different markers (MLH1, MSH6, MSH2, PMS2).

2 oarrays for loss of MLH1, MSH2, MSH6, and/or PMS2.

3 germ line mutations in MLH1, MSH2, MSH6, and PMS2.

4 ast one related gene resembles the 3' end of PMS2.

5 proapoptotic function by cisplatin requires PMS2.

6 l change for Mlh1 was more apparent than for Pms2.

7 ferential conformational changes in Mlh1 and Pms2.

8 e role of Msh2 differs from that of Mlh1 and Pms2.

9 showed more tumor foci with loss of PMS1 and PMS2.

10 tch repair proteins MLH1, MSH2, MSH6, and/or PMS2.

11 n both Apc and the DNA mismatch repair gene, Pms2.

12 repair gene Xpa or the mismatch repair gene Pms2.

13 homologues of the human genes MLH1, PMS1 and PMS2.

14 mismatch repair genes MSH2, MLH1, PMS1, and PMS2.

15 in mice lacking the DNA mismatch repair gene Pms2.

16 re distinct from those deficient in msh2 and pms2.

17 and PMS1 outranked known namesakes MSH6 and PMS2.

18 MSH6, 7 (30%) MLH1, 3 (13%) MSH2, and 2 (9%) PMS2.

19 PALB2, PTEN, NBN, RAD51C, RAD51D, MSH6, and PMS2.

20 ndrome-associated genes MLH1, MSH2, MSH6 and PMS2.

21 he endonuclease functions of its MMR partner PMS2.

22 mismatch repair genes: MSH2, MLH1, MSH6, and PMS2.

23 reened for MLH1 methylation and mutations in PMS2.

24 o mismatch repair genes MLH1, MSH2, MSH6 and PMS2.

25 MSH2; 1, MSH2/monoallelic MUTYH; 2, MSH6; 5, PMS2); 1 patient had the APC c.3920T>A, p.I1307K mutatio

26 In this study we demonstrate that the pms2-1 and pms2-2 alleles arise from missense mutations

27 , 11 in MSH2 (21%), 3 in MSH6 (6%), and 6 in PMS2 (12%); 8 mutations were detected in more than 1 ind

28 his study we demonstrate that the pms2-1 and pms2-2 alleles arise from missense mutations in the MLH1

29 One of these alleles, pms2-2, causes the same amino acid substitution in a hig

30 in high-penetrance CRC genes (5, APC; 1, APC/PMS2; 2, biallelic MUTYH; 1, SMAD4); 13 patients had mut

31 vival at age 15 years 63% [95% CI 55-73] for PMS2, 49% [35-68] for MSH6, 19% [6-66] for MLH1, and 0%

32 Mice deficient in Pms2, a mammalian homolog of bacterial mutL, develop can

33 re pathogenic variants in the genes MSH6 and PMS2 account for the majority of cases.

34 -) mice, indicating that a single functional Pms2 allele is sufficient to generate normal levels of s

35 Beyond its endonuclease role, Mlh1-Pms1/MLH1-PMS2 also has ATPase activity, which genetic studies sug

36 It is shown that postmeiotic segregation 2 (PMS2), an MMR protein, is required for cisplatin-induced

37 Here, we describe an interaction between PMS2, an MMR protein, and p73.

38 which are potentially targetable, as well as PMS2 and BRCA1, are among the most frequently mutated DD

39 sequence identity with exons 9 and 11-15 of PMS2 and emanating from a locus close to PMS2 in chromos

40 n model, PREMM5, that incorporates the genes PMS2 and EPCAM to provide comprehensive LS risk assessme

41 develop intestinal tumors, mice deficient in Pms2 and heterozygous for Min, an allele of Apc, develop

42 ll lines derived from mice deficient for the PMS2 and MLH1 mismatch repair proteins.

43 e base-pair substitutions increased when the Pms2 and Mlh1 null cells were treated with ultraviolet r

44 discussed with regards to the roles for the PMS2 and MLH1 proteins in preventing spontaneous and gen

45 nvolved in mismatch repair and at least two, Pms2 and Mlh1, are essential for meiotic progression in

46 lease and mismatch repair activities of MLH1-PMS2 and MLH1-PMS1, respectively.

47 ation in two MutL types of MMR deficiencies, Pms2 and Mlh1.

48 smatch repair complex MutLalpha, composed of PMS2 and MLH1.

49 a CRISPR-Cas9 knockout approach we show that PMS2 and MLH3, the constituents of MutLalpha and MutLgam

50 proved OS was seen in patients with low ATM, PMS2 and MLH3.

51 Mice with mutations in Mlh1, Pms2 and Msh5 have defects in meiosis suggesting unique

52 smatch repair proteins MSH2, MSH6, MLH1, and PMS2 and occurs by a mechanism that is distinct from tha

53 o cisplatin enhances the association between PMS2 and p73.

54 Germline mutations in the human MSH2, MLH1, PMS2 and PMS1 DNA mismatch repair (MMR) gene homologues

55 ents whose colon tumors stained negative for PMS2 and positive for MLH1 by immunohistochemistry.

56 analysis we show here that human MSH2, MLH1, PMS2 and proliferating cell nuclear antigen (PCNA) can b

57 Mutations within this motif in human PMS2 and Saccharomyces cerevisiae PMS1 disrupted the end

58 ignificant differences were observed between Pms2(+/+) and Pms2(+/-) mice, indicating that a single f

59 in immortalized MMR deficient (Mlh1(-/-) and Pms2(-/-)) and WT MEFs.

60 h mutations in MSH6, and 2 with mutations in PMS2) and 10 subjects had pathogenic variants associated

61 Mutated gene (MLH1, MSH2, MSH6, and/or PMS2) and type of mutation (truncating, splicing, or lar

62 s, it causes a reduction of XPA, XPC, hOGG1, PMS2, and MLH1 proteins; this effect, however, can be ne

63 tS (MSH2, MSH3, and MSH6), MutL (MLH1, PMS1, PMS2, and MLH3), and LIG1 resulted in characteristic MMR

64 1, BRCA2, BRIP1, RAD51C, RAD51D, MSH2, MLH1, PMS2, and MSH6) bring the total number of genes suspecte

65 analysis, we detected loss among MSH2, MLH1, PMS2, and PMS1 proteins in DU145, LNCaP, p69SV40T, M2182

66 1, EPCAM, MLH1, MSH2, MSH6, biallelic MUTYH, PMS2, and TP53] and eight category B genes [ATM, BRIP1,

67 Pms2- and Mlh-1-deficient mice also resemble Msh2-defici

68 We found that both Pms2- and Mlh1-deficient mice can somatically hypermutat

69 T (hMGMT) transgenic mice were mated and the PMS2-/- and PMS2+/+ with or without hMGMT offspring were

70 h1(-/-) mice was 2- to 3-fold higher than in Pms2(-/-) animals.

71 of some residual DNA repair capacity in the Pms2(-/-) animals.

72 ions in T cells and fibroblasts of 129 x C3H Pms2-/-Aprt+/- mice.

73 The MMR proteins MSH2, MSH6, MLH1, and PMS2 are similarly detected in both cell lines.

74 Mice defective in the MMR gene PMS2 are susceptible to spontaneous thymic lymphoma and

75 PMS2-related genes resembling the 5' end of PMS2, at least one related gene resembles the 3' end of

76 ssion of DNA repair genes (MLH1, MLH3, PMS1, PMS2, ATR, PRKDC, ATM, BRCA2) associated with MSI-H.

77 n induction of chromosome gaps and breaks in PMS2-, BRCA1-, MSH2-, MLH1-, FHIT-, and TP53-deficient c

78 Correspondingly, PMS2 but not PMS2(R20Q) enhanced the cytotoxic effect of

79 ers of these families, MSH2, MSH6, MLH1, and PMS2, but not MSH3, are responsible for hereditary non-p

80 e-associated tumors showing isolated loss of PMS2 by immunohistochemistry.

81 Amino acid substitution mutations within a PMS2 C-terminal (721)QRLIAP motif attenuate or abolish h

82 overall AA detection rate compared with MSH6/PMS2 carriers (14.5% vs 11.9%; P = .04) and showed highe

83 stability of the core MMR proteins (MLH1 and PMS2) caused by elevated basal caspase-dependent proteol

84 lt-onset cancer predisposition genes (BRCA2, PMS2, CHEK2, and MUTYH) were identified in 5 of 56 (8.9%

85 Contributions by both MLH1/MLH3 and MLH1/PMS2 complexes to mechanisms of mismatch repair-mediated

86 ate IR further showed that nullizygosity for Pms2 confers increased survival on cells in both wild-ty

87 ll colonies analyzed (cell lines HCT 116 and PMS2-/-) contained both the wild-type and mutated PBS, t

88 These results suggest that PMS2 contributes to genome integrity not only through DN

89 eporter gene and an out-of-frame Cre allele (Pms2(cre)) that stochastically becomes functional by a f

90 These data suggest that PMS2 defective lymphomas may arise by the concerted acti

91 of the two processes, whereas the fact that PMS2 deficiency affects only switch recombination may re

92 Although Pms2 deficiency clearly increases adenoma formation in t

93 leles is a maternal effect that results from Pms2 deficiency during the early cleavage divisions.

94 utation show many parallels, we confirm that PMS2 deficiency has no major effect on the pattern of nu

95 tion in the early mouse embryo suggests that Pms2 deficiency is a maternal effect, one of a limited n

96 s, the mutator phenotype as a consequence of PMS2 deficiency is tissue-dependent, which may be relate

97 B cells in comparison with Msh2-, Mlh1-, and Pms2-deficient B cells.

98 By contrast, 23% of junctions from Mlh1- and Pms2-deficient cells occurred at unusually long stretche

99 Interestingly, Pms2-deficient males display sterility associated with a

100 r/acceptor homology at switch junctions from PMS2-deficient mice and propose that class switching can

101 Whereas Pms2-deficient mice do not develop intestinal tumors, mi

102 However, variable genes from PMS2-deficient mice had significantly more adjacent base

103 und in variable genes from XPA-deficient and PMS2-deficient mice, indicating that neither nucleotide

104 ncer susceptibility in Mlh1- versus Mlh3- or Pms2-deficient mice.

105 When expressed in Pms2-deficient mouse fibroblasts, human PMS2(R20Q) but n

106 mutable to IR, we compared IR mutagenesis of Pms2-deficient versus wild-type transgenic mice carrying

107 ermutation mechanism and then processed by a PMS2-dependent pathway.

108 tch repair (MMR) genes (MLH1, MSH2, MSH6, or PMS2) develop a rare but severe variant of Lynch syndrom

109 es of Msh2 and the MutL homologues, Mlh1 and Pms2, differ.

110 nuclear localization of MutLalpha (the MLH1-PMS2 dimer).

111 Furthermore, Mlh3;Pms2 double-deficient mice have tumor susceptibility, sh

112 between Mlh1(-/-) animals and Mlh1(-/-) and Pms2(-/-) double knockout mice revealed little differenc

113 nuclease active site has been localized to a PMS2 DQHA(X)(2)E(X)(4)E motif.

114 ease that is dependent on the integrity of a PMS2 DQHA(X)2E(X)4E motif.

115 Therefore, the PMS2 endonuclease activity has distinct biological funct

116 ed mismatch repair genes ( MLH1, MSH2, MSH6, PMS2, EPCAM).

117 the mismatch repair genes (MLH1, MSH2, MSH6, PMS2, EPCAM).

118 umor DNA was sequenced for MLH1, MSH2, MSH6, PMS2, EPCAM, POLE, and POLD1 with ColoSeq and mutation f

119 but selectively loses MLH1 and consequently PMS2 expression following inflammation.

120 Immunohistochemistry showed absent PMS2 expression in all tumors and normal tissue.

121 Data were collected from 98 PMS2 families ascertained from family cancer clinics tha

122 tic stability, we analyzed F(1) progeny from Pms2(-/-) female mice mated with wild-type males.

123 n detection methods can discern mutations in PMS2 from mutations in its pseudogenes, more mutation ca

124 Mice carrying a mutation in the Pms2 gene are predisposed to lymphomas and other tumors.

125 ent of the MMR complex, yet mutations in the PMS2 gene are rare in the etiology of hereditary nonpoly

126 nch syndrome cases for MSH2, MLH1, MSH6, and PMS2 gene defects.

127 The Pms2 gene has been implicated in hereditary colon cancer

128 e deletion, which included exons 9-15 of the PMS2 gene, and all coding regions of oncomodulin, TRIAD3

129 -line mutations in the MLH1, MSH2, MSH6, and PMS2 genes with the use of immunohistochemical staining

130 The clinical consequences of PMS2 germline mutations are poorly understood compared w

131 cted one unrelated individual with biallelic PMS2 germline mutations, representing constitutional mis

132 disrupted allele of the mismatch repair gene Pms2 have a mutator phenotype.

133 We found that MLH1 and PMS2 have functional nuclear localization signals (NLS)

134 Human MutLalpha (MLH1-PMS2 heterodimer) harbors a latent endonuclease that is

135 or mutations that inactivate MutLalpha (MLH1*PMS2 heterodimer).

136 Eukaryotic MutLalpha (mammalian MLH1-PMS2 heterodimer; MLH1-PMS1 in yeast) functions in early

137 c lymphomagenesis was efficiently blocked in PMS2+/+/hMGMT+ mice with rapid repair of O6-meG.

138 The incidence of lymphomas in PMS2-/-/hMGMT+ mice was reduced to 80% (P < 0.01) and me

139 This motif is conserved in eukaryotic PMS2 homologs and in MutL proteins from a number of bact

140 our knowledge this is the first time a human PMS2 homologue has been demonstrated to stimulate a PcrA

141 were repaired by wild-type cells but not by Pms2(-/-) human or murine cells.

142 in 99 (89%) of 111 cases demonstrating MLH1/PMS2 IHC loss; all were germline MLH1 mutation negative.

143 of PMS2 and emanating from a locus close to PMS2 in chromosome 7p.

144 rade glioma (HGG), and medulloblastoma (MB), PMS2 in HGG and non-Hodgkin lymphoma (NHL), MLH1 in HGG,

145 studies in mice confirmed roles for Mlh1 and Pms2 in mammalian meiosis.

146 of Msh2, Mlh1, Gtmbp (also known as Msh6) or Pms2 in mice leads to hereditary predisposition to intes

147 reduced, consistent with destabilization of PMS2 in the absence of its heterodimer partner, MLH1.

148 To study the role of Pms2 in the maintenance of in vivo genomic integrity in

149 ences, consistent with an essential role for PMS2 in the repair of replication slippage errors.

150 istent with nonoverlapping roles for p53 and PMS2 in the X-ray response.

151 lease of the MutL homologs PMS1 in yeast and PMS2 in vertebrates.

152 ents), APC (in 6), BRCA2 (in 6), NF1 (in 4), PMS2 (in 4), RB1 (in 3), and RUNX1 (in 3).

153 match repair proteins (MLH1, MSH2, MSH6, and PMS2) in these tumors.

154 To determine the effect of Pms2 inactivation on genomic integrity in vivo, hybrid t

155 mouse fibroblasts, human PMS2(R20Q) but not PMS2 interfered with the apoptotic response to cisplatin

156 e alleles present in small patches of normal Pms2 -/- intestines revealed a general increase in genet

157 d by mismatch repair (MMR) proteins MLH1 and PMS2 is a major component of the MMR complex, yet mutati

158 Pms2 is a MutL homologue that plays a critical role in t

159 Although MLH1/PMS2 is generally thought to have the major MutL activit

160 The human PMS2 is highly polymorphic, with at least 12 known nonsy

161 asked whether nuclear transport of MLH1 and PMS2 is limiting for the nuclear localization of MutLalp

162 f other MMR genes, including Msh2, Msh6, and Pms2, is not altered at the mRNA level.

163 utLalpha, a heterodimer composed of Mlh1 and Pms2, is the major MutL activity in mammalian DNA mismat

164 e DNA methyltransferase (MGMT), heterozygous PMS2 knockout mice and human MGMT (hMGMT) transgenic mic

165 To determine the sensitivity of PMS2 knockout mice to environmental carcinogens and the

166 ynch syndrome-associated variants of MSH6 or PMS2, later initiation of surveillance at 35 and 40 year

167 mismatch-repair genes MLH1, MSH2, MSH6, and PMS2 lead to the development of the Lynch syndrome (here

168 clude changes in MLH1, MSH2, MSH3, MSH6, and PMS2 levels across various primary cell lines, independe

169 elator desferrioxamine also reduced MLH1 and PMS2 levels, in keeping with low oxygen tension being th

170 ucted that carry targeted disruptions at the Pms2 loci along with a chromosomally integrated mutation

171 additional modifier effects at the PMS1 and PMS2 loci and implicated a potential second locus on chr

172 This complex is up-regulated in Pms2-/- males, but not females, providing an explanation

173 Functional redundancy among Mlh3, Pms1 and Pms2 may explain why neither Pms1 nor Pms2 mutant mice d

174 ismatch repair genes MLH1, MSH2, MLH3, MSH6, PMS2, MGMT and MLH3 via methylation specific multiplex l

175 ferences were observed between Pms2(+/+) and Pms2(+/-) mice, indicating that a single functional Pms2

176 Furthermore, we show that Ung(-/-)Pms2(-/-) mice display a 50% reduction in mutations at A

177 Relevant to this idea, we observed that Pms2(-/-) mice exhibit almost normal levels of Mlh1p, wh

178 U-treated PMS2-/- mice, compared to wildtype PMS2+/+ mice (100 vs 52%; P < 0.001).

179 less than 20% of the DAP(r) mutant clones in Pms2+/+ mice, was predominant in the mutant T cell clone

180 ymphomas was also significantly shortened in PMS2-/- mice (81 vs 102 days, P < 0.01).

181 Fibroblasts of Pms2-/- mice exhibited only a modest increase in the fre

182 thymic lymphomas was observed in MNU-treated PMS2-/- mice, compared to wildtype PMS2+/+ mice (100 vs

183 In contrast to Pms2-/- mice, Pms2EK/EK male mice were fertile, indicati

184 xplanation for the sexual dimorphism seen in Pms2-/- mice.

185 predominant in the mutant T cell clones from Pms2-/- mice.

186 ed to the tissue-specific tumor proneness of Pms2-/- mice.

187 incompletely blocked MNU lymphomagenesis in PMS2-/- mice.

188 number of colon adenomas relative to Min and Pms2+/-;Min mice.

189 Mice null for the Pms2 mismatch repair (MMR) gene exhibit a predisposition

190 D50, and NBN MRN complex genes; the MLH1 and PMS2 mismatch repair genes; and NF1 were not associated

191 V genes from mice deficient for the MSH2 and PMS2 mismatch repair proteins have frequencies of mutati

192 Additional mismatch repair enzymes (PMS2, MLH1) were targeted, apparently independently.

193 f one of three MMR genes in mammalian cells: Pms2, Mlh1, or Msh2.

194 erize to form three distinct complexes: MLH1/PMS2, MLH1/MLH3, and MLH1/PMS1.

195 wild-type cell lines from related mice, the Pms2-, Mlh1-, or Msh2-nullizygous cell lines were found

196 These results demonstrate that Pms2/Mlh1 and multiple uracil glycosylases act jointly,

197 Paradoxically, the MMR-nicking complex Pms2/Mlh1 is apparently dispensable for A-T mutagenesis.

198 icant promoter methylation was seen in MLH1, PMS2, MLH3 and MSH3 as well as significant heterogeneity

199 ded CAG.CTG repeat in mice deficient for the Pms2 MMR gene.

200 Immunohistochemistry (IHC) results of MLH1, PMS2, MSH2 and MSH6 were obtained from medical records a

201 H6 mutations were most frequent, followed by PMS2, MSH2, MLH1, and EPCAM mutations, respectively.

202 ith microsatellite instability, namely MLH1, PMS2, MSH2, MSH6, P53 and PTEN.

203 e hPMS2 cDNA by stable transfection into the PMS2 mutant HEC-1-A cell line.

204 s1 and Pms2 may explain why neither Pms1 nor Pms2 mutant mice develop colon cancer, and why PMS1 and

205 to 68 years) and other family members with a PMS2 mutation (mean, 58 years; range, 31 to 86 years; P

206 We performed PMS2 mutation analysis using long-range polymerase chain

207 represents a novel phenotype for homozygous PMS2 mutation and perhaps the most severe colorectal can

208 eling and cancer surveillance guidelines for PMS2 mutation carriers are proposed.

209 study was to define the cancer risk faced by PMS2 mutation carriers.

210 described, little is known about disease in PMS2 mutation carriers.

211 linical characteristics of a large series of PMS2 mutation carriers.

212 risks embody the isolated risk of carrying a PMS2 mutation, and it should be noted that we observed a

213 e defect, mostly involving MSH2 or MLH1; one PMS2 mutation, one MLH1 epimutation, and no MSH6 mutatio

214 Prediction was more difficult for PMS2 mutations (AUC, 0.64; 95% CI, 0.60 to 0.68) than fo

215 mice develop colon cancer, and why PMS1 and PMS2 mutations are only rarely found in HNPCC families.

216 sted that contrary to the Knudson principle, PMS2 mutations cause hereditary nonpolyposis colorectal

217 PMS2 mutations contribute significantly to Lynch syndrom

218 formation about the clinical significance of PMS2 mutations is crucial for appropriate counseling.

219 S and suggest that individuals with MSH6 and PMS2 mutations may present with a hereditary breast and

220 Germ-line PMS2 mutations were detected in 62% of probands (n = 55

221 MSH6 and PMS2 mutations were more frequent than MLH1 and MSH2 mut

222 cancer only to those with CRC only, MSH6 and PMS2 mutations were more frequent than MLH1 and MSH2 mut

223 Among families with monoallelic PMS2 mutations, 65.5% met revised Bethesda guidelines.

224 As candidates for PMS2 mutations, we selected seven patients whose colon t

225 developing AAs compared with those with MSH6/PMS2 mutations, with MSH6 carriers exhibiting an interme

226 PMS2 mutations-and perhaps other homozygous mismatch rep

227 on detection, resulting in underdiagnosis of PMS2 mutations.

228 s were observed in Msh2 (MutS homologue) and Pms2 (MutL homologue) MMR-deficient mice.

229 of MutLalpha demonstrated that both Mlh1 and Pms2 N-terminal domains undergo ATP-induced conformation

230 1 (n = 306), MSH2 (n = 354), MSH6 (n = 177), PMS2 (n = 141), and EPCAM (n = 22).

231 ome (LS) genes: MLH1 (n = 10), MSH6 (n = 2), PMS2 (n = 2), and MSH2 (n = 1).

232 hed in tumors deficient in MSH6 (n = 35) and PMS2 (n = 9) after targeted sequencing of samples with a

233 creased 33-fold and 3.6-20-fold for Mlh1 and Pms2 null cell lines, respectively, when compared with a

234 For the Pms2 null cells this increase resulted from both intrage

235 54% of small events) were predominant in the Pms2 null cells whereas G:C-->A:T transitions (36%) were

236 ith genotypes of either wild type, p53 null, Pms2 null, or double null.

237 xpansion was reduced by approximately 50% in Pms2-null mice.

238 In Pms2 nullizygous animals, the mutation frequency in the

239 SH2 and/or MSH6 expression, isolated loss of PMS2 or loss of MLH1 without MLH1 promoter hypermethylat

240 n patients exhibiting loss of MSH6, MSH2, or PMS2 or loss of MLH1/PMS2 with absence of MLH1 methylati

241 ot change the expression of XPA, XPC, hOGG1, PMS2 or MLH1 genes, it causes a reduction of XPA, XPC, h

242 rains homozygous for knockouts of either the Pms2 or Mlh1 MMR gene develop cancer but exhibit very di

243 Mice that are deficient in either the Pms2 or Msh2 DNA mismatch repair genes have microsatelli

244 H2 variants caused earlier cancer onset than PMS2 or MSH6 variants, and inferior survival (overall su

245 redicted to catalyze ATP hydrolysis of Mlh1, Pms2, or both.

246 c B cells from mice deficient in Msh2, Mlh1, Pms2, or Mlh1 and Pms2 were stimulated in culture with l

247 rtial functional redundancy between MLH3 and PMS2 orthologues for mutation avoidance and show a role

248 mmalian MutL homologs (MLH1, MLH3, PMS1, and PMS2) participate in a variety of events, including post

249 We find that founder mutations in MSH6 and PMS2 prevail in Iceland unlike most other populations.

250 Because the absence of MSH2 and PMS2 produced different mutational spectra, we examined

251 However, levels of the PMS2 protein are reduced, consistent with destabilizatio

252 stochemistry (IHC) for MLH1, MSH2, MSH6, and PMS2 protein expression and microsatellite instability (

253 In two additional patients, PMS2 protein from one allele also was abrogated.

254 These mutations abrogated PMS2 protein in germline cells by Western analysis.

255 s was not affected by antibodies against the PMS2 protein, which inhibited long-patch mismatch repair

256 an MutSalpha (MSH2-MSH6) and MutLalpha (MLH1-PMS2) proteins, and in vitro mismatch repair and excisio

257 CA1, BRCA2, CDKN2A, MLH1, MSH2, MSH6, PALB2, PMS2, PRSS1, STK11, and TP53 in patients with pancreatic

258 CDH1, CHEK2, EPCAM, MLH1, MSH2, MSH6, MUTYH, PMS2, PTEN, SMAD4, STK11, and TP53 genes are associated

259 d in Pms2-deficient mouse fibroblasts, human PMS2(R20Q) but not PMS2 interfered with the apoptotic re

260 Correspondingly, PMS2 but not PMS2(R20Q) enhanced the cytotoxic effect of cisplatin me

261 Because PMS2(R20Q) lacks proapoptotic activity, this polymorphic

262 We show here that the PMS2(R20Q) variant is defective in activating p73-depend

263 with the idea that dimerization of MLH1 and PMS2 regulates nuclear import by unmasking the NLS.

264 in addition to several previously described PMS2-related genes resembling the 5' end of PMS2, at lea

265 Mutation detection in PMS2 requires haploid DNA.

266 patients with pathogenic variants in MSH6 or PMS2, respectively.

267 of the four MutL homologues (Mlh1, Mlh3, and Pms2) result in meiotic defects.

268 evance: BRCA1, BRCA2, MLH1, MSH2, MSH6, APC, PMS2, SCN5A-SCN10A, and PKI3CA.

269 Cells with either p53 or Pms2 separately disrupted showed reduced levels of apopt

270 ny mutagenic treatment, mice nullizygous for Pms2 showed a 100-fold elevation in mutation frequency i

271 re, we demonstrate that MSH2, MSH6, MLH1 and PMS2, specifically, are involved in the activation of th

272 erminal endonuclease domain of the MutLalpha PMS2 subunit.

273 H1 subunit and greatly reduced levels of the PMS2 subunit.

274 s protected at lower ATP concentrations than Pms2, suggesting Mlh1 binds ATP with higher affinity.

275 rupting MLH1 and three mutations in MSH6 and PMS2 that increase endometrial, colorectal, brain and ov

276 e mismatch repair genes MLH1, MSH2, MSH6, or PMS2, that cause predisposition to various cancers, pred

277 Inactivating Pms2, the human homologue of yeast Pms1, increases the c

278 the four MutL homologs, Mlh1, Mlh3, Pms1 and Pms2, three are involved in mismatch repair and at least

279 ations in BRCA1, BRCA2, MLH1, MSH2, MSH6 and PMS2 to invasive epithelial ovarian cancer (EOC) in the

280 abilization of p73 and the redistribution of PMS2 to the nuclear compartment.

281 nt of the Mlh1-Pms1 endonuclease (human MLH1-PMS2) to mispaired DNA.

282 n, RFC, PCNA, RPA, and Mlh1-Pms1 (human Mlh1-Pms2) under conditions lacking Exo1, Rad27, or strand-di

283 utations in MMR genes (MLH1, MSH2, MSH6, and PMS2) using databases from 13 US referral centers.

284 d the APC c.3920T>A, p.I1307K mutation and a PMS2 variant; 9 patients (18.8%) had double somatic MMR

285 For individuals with PMS2 variants, hyst-BSO at age 50 years was optimal and

286 id early menopause, and for individuals with PMS2 variants, the findings suggest that hyst-BSO may be

287 Promoter methylation in MLH1, MLH3, MSH3 and PMS2 was also found to be significantly associated with

288 The DNA mismatch repair protein PMS2 was recently found to encode a novel endonuclease a

289 homolog, mismatch repair system component 2 (PMS2) was performed.

290 or previously described missense variants of PMS2 were detected, but their pathogenicity is undetermi

291 o haploidy, truncating germline mutations of PMS2 were found in two patients (2192delTAACT and deleti

292 the p53 gene or the MutL homologue MMR gene Pms2 were interbred and primary fibroblasts were establi

293 e deficient in Msh2, Mlh1, Pms2, or Mlh1 and Pms2 were stimulated in culture with lipopolysaccharide

294 nt cell clones analyzed (cell lines HeLa and PMS2+/+) were repaired, while 75% were not.

295 repair (MMR) proteins MLH1, MSH2, MSH6, and PMS2; when the second allele becomes mutated, cancer can

296 loss of MSH6, MSH2, or PMS2 or loss of MLH1/PMS2 with absence of MLH1 methylation.

297 l SCAs (p = 2.22 x 10(-4) ) and rs1805323 in PMS2 with HD+SCAs (p = 3.14 x 10(-5) ), all in the same

298 ansgenic mice were mated and the PMS2-/- and PMS2+/+ with or without hMGMT offspring were treated at

299 r eukaryotic pathway, recruit Mlh1-Pms1/MLH1-PMS2 (yeast/human) complexes, which nick the newly repli

300 gen (PCNA)-stimulated endonuclease Mlh1-Pms1/PMS2 (yeast/human), which nicks the DNA to allow downstr