DNA mismatch repair guards the integrity of the genome of almost all organisms by correcting DNA biosynthetic errors and by ensuring the fidelity of homologous genetic recombination. MutL is one of the important prote...DNA mismatch repair guards the integrity of the genome of almost all organisms by correcting DNA biosynthetic errors and by ensuring the fidelity of homologous genetic recombination. MutL is one of the important proteins involved in mismatch repair system. It has been suggested to function as a master coordinator or molecular matchmaker because it interacts physically with MutS, the endonuclease MutH, and DNA helicase UvrD. It also binds to DNA and has an ATPase activity. MutL defective bacteria strains have elevated mutation rates and it has been reported recently that MutL defect may have an important impact on bacterial evolution.展开更多
目的分析淋巴结转移性结直肠癌中DNA错配修复基因(mismatch repair,MMR)系统MLH1(Mut L homolog1)和MSH2(Mut S homolog 2)基因的表达水平及临床意义。方法选取2015年6月至2017年4月收治的120例淋巴结转移性结直肠癌患者为研究对象,同...目的分析淋巴结转移性结直肠癌中DNA错配修复基因(mismatch repair,MMR)系统MLH1(Mut L homolog1)和MSH2(Mut S homolog 2)基因的表达水平及临床意义。方法选取2015年6月至2017年4月收治的120例淋巴结转移性结直肠癌患者为研究对象,同期选取120例无淋巴结转移的结直肠癌患者为对照;通过免疫组化法、实时荧光定量PCR法(q RT-PCR)、Western blot法,分别检测两组正常癌旁组织及病灶组织中MLH1、MSH2蛋白阳性表达缺失率,MLH1、MSH2 m RNA及蛋白表达水平。结果两组患者病灶组织MLH1、MSH2蛋白阳性表达缺失率均高于癌旁组织,而MLH1、MSH2 m RNA及蛋白相对表达水平均低于癌旁组织,差异均有统计学意义(P均<0.05);淋巴结转移性结直肠癌组病灶组织MLH1、MSH2蛋白阳性表达缺失率均高于无淋巴结转移组,MLH1、MSH2 m RNA及蛋白相对表达水平均低于无淋巴结转移组,差异均有统计学意义(P均<0.05);两组癌旁组织MLH1、MSH2蛋白阳性表达缺失率、MLH1、MSH2 m RNA及蛋白相对表达水平比较差异均无统计学意义(P均>0.05);MLH1、MSH阳性表达缺失率与淋巴结转移性结直肠癌患者的肿瘤直径、浸润深度、分化程度及淋巴结转移数有密切关系(P均<0.01),而与年龄无关(P>0.05)。结论淋巴结转移性结直肠癌中MLH1、MSH2表达水平显著降低,推测其在结直肠癌由无淋巴结转移进展为发生淋巴结转移中具有重要作用。展开更多
DNA mismatch repair （MMR） is a highly conserved biological pathway that plays a key role in maintaining genomic stability. The specificity of MMR is primarily for base-base mismatches and insertion/deletion mispairs...DNA mismatch repair （MMR） is a highly conserved biological pathway that plays a key role in maintaining genomic stability. The specificity of MMR is primarily for base-base mismatches and insertion/deletion mispairs generated during DNA replication and recombination. MMR also suppresses homeologous recombination and was recently shown to play a role in DNA damage signaling in eukaryotic cells. Escherichia coli MutS and MutL and their eukaryotic homologs, MutSα and MutLα, respectively, are key players in MMR-associated genome maintenance. Many other protein components that participate in various DNA metabolic pathways, such as PCNA and RPA, are also essential for MMR. Defects in MMR are associated with genome-wide instability, predisposition to certain types of cancer including hereditary non-polyposis colorectal cancer, resistance to certain chemotherapeutic agents, and abnormalities in meiosis and sterility in mammalian systems.展开更多
文摘DNA mismatch repair guards the integrity of the genome of almost all organisms by correcting DNA biosynthetic errors and by ensuring the fidelity of homologous genetic recombination. MutL is one of the important proteins involved in mismatch repair system. It has been suggested to function as a master coordinator or molecular matchmaker because it interacts physically with MutS, the endonuclease MutH, and DNA helicase UvrD. It also binds to DNA and has an ATPase activity. MutL defective bacteria strains have elevated mutation rates and it has been reported recently that MutL defect may have an important impact on bacterial evolution.
文摘目的分析淋巴结转移性结直肠癌中DNA错配修复基因(mismatch repair,MMR)系统MLH1(Mut L homolog1)和MSH2(Mut S homolog 2)基因的表达水平及临床意义。方法选取2015年6月至2017年4月收治的120例淋巴结转移性结直肠癌患者为研究对象,同期选取120例无淋巴结转移的结直肠癌患者为对照;通过免疫组化法、实时荧光定量PCR法(q RT-PCR)、Western blot法,分别检测两组正常癌旁组织及病灶组织中MLH1、MSH2蛋白阳性表达缺失率,MLH1、MSH2 m RNA及蛋白表达水平。结果两组患者病灶组织MLH1、MSH2蛋白阳性表达缺失率均高于癌旁组织,而MLH1、MSH2 m RNA及蛋白相对表达水平均低于癌旁组织,差异均有统计学意义(P均<0.05);淋巴结转移性结直肠癌组病灶组织MLH1、MSH2蛋白阳性表达缺失率均高于无淋巴结转移组,MLH1、MSH2 m RNA及蛋白相对表达水平均低于无淋巴结转移组,差异均有统计学意义(P均<0.05);两组癌旁组织MLH1、MSH2蛋白阳性表达缺失率、MLH1、MSH2 m RNA及蛋白相对表达水平比较差异均无统计学意义(P均>0.05);MLH1、MSH阳性表达缺失率与淋巴结转移性结直肠癌患者的肿瘤直径、浸润深度、分化程度及淋巴结转移数有密切关系(P均<0.01),而与年龄无关(P>0.05)。结论淋巴结转移性结直肠癌中MLH1、MSH2表达水平显著降低,推测其在结直肠癌由无淋巴结转移进展为发生淋巴结转移中具有重要作用。
文摘DNA mismatch repair （MMR） is a highly conserved biological pathway that plays a key role in maintaining genomic stability. The specificity of MMR is primarily for base-base mismatches and insertion/deletion mispairs generated during DNA replication and recombination. MMR also suppresses homeologous recombination and was recently shown to play a role in DNA damage signaling in eukaryotic cells. Escherichia coli MutS and MutL and their eukaryotic homologs, MutSα and MutLα, respectively, are key players in MMR-associated genome maintenance. Many other protein components that participate in various DNA metabolic pathways, such as PCNA and RPA, are also essential for MMR. Defects in MMR are associated with genome-wide instability, predisposition to certain types of cancer including hereditary non-polyposis colorectal cancer, resistance to certain chemotherapeutic agents, and abnormalities in meiosis and sterility in mammalian systems.
