人源PMS2中的E705K突变对错配修复发挥隐性而非显性作用。
The E705K mutation in hPMS2 exerts recessive, not dominant, effects on mismatch repair.
作者信息
Deschênes Suzanne M, Tomer Guy, Nguyen Megan, Erdeniz Naz, Juba Nicole C, Sepúlveda Natalia, Pisani Jenna E, Liskay R Michael
机构信息
Department of Biology, Sacred Heart University, 5151 Park Ave., Fairfield, CT 06825, USA.
出版信息
Cancer Lett. 2007 May 8;249(2):148-56. doi: 10.1016/j.canlet.2006.08.008. Epub 2006 Oct 9.
Abstract
The hPMS2 mutation E705K is associated with Turcot syndrome. To elucidate the pathogenesis of hPMS2-E705K, we modeled this mutation in yeast and characterized its expression and effects on mutation avoidance in mammalian cells. We found that while hPMS2-E705K (pms1-E738K in yeast) did not significantly affect hPMS2 (Pms1p in yeast) stability or interaction with MLH1, it could not complement the mutator phenotype in MMR-deficient mouse or yeast cells. Furthermore, hPMS2-E705K/pms1-E738K inhibited MMR in wild-type (WT) mammalian cell extracts or yeast cells only when present in excess amounts relative to WT PMS2. Our results strongly suggest that hPMS2-E705K is a recessive loss-of-function allele.
摘要
人源PMS2基因的E705K突变与Turcot综合征相关。为阐明hPMS2-E705K的发病机制，我们在酵母中模拟了这种突变，并对其在哺乳动物细胞中的表达及对避免突变的影响进行了表征。我们发现，虽然hPMS2-E705K（酵母中的pms1-E738K）对hPMS2（酵母中的Pms1p）的稳定性或与MLH1的相互作用没有显著影响，但它不能弥补MMR缺陷的小鼠或酵母细胞中的突变体表型。此外，只有当相对于野生型PMS2过量存在时，hPMS2-E705K/pms1-E738K才会抑制野生型（WT）哺乳动物细胞提取物或酵母细胞中的错配修复。我们的结果有力地表明，hPMS2-E705K是一个隐性功能丧失等位基因。
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本文引用的文献
1
Endonucleolytic function of MutLalpha in human mismatch repair.MutLα在人类错配修复中的核酸内切酶功能。
Cell. 2006 Jul 28;126(2):297-308. doi: 10.1016/j.cell.2006.05.039.
2
PMS2 mutations in childhood cancer.儿童癌症中的PMS2突变。
J Natl Cancer Inst. 2006 Mar 1;98(5):358-61. doi: 10.1093/jnci/djj073.
3
DNA mismatch repair: functions and mechanisms.DNA错配修复：功能与机制
Chem Rev. 2006 Feb;106(2):302-23. doi: 10.1021/cr0404794.
4
Truncation of the C-terminus of human MLH1 blocks intracellular stabilization of PMS2 and disrupts DNA mismatch repair.人源MLH1 C末端的截短会阻碍PMS2在细胞内的稳定，并破坏DNA错配修复。
DNA Repair (Amst). 2006 Mar 7;5(3):347-61. doi: 10.1016/j.dnarep.2005.11.001. Epub 2005 Dec 9.
5
Novel PMS1 alleles preferentially affect the repair of primer strand loops during DNA replication.新型PMS1等位基因在DNA复制过程中优先影响引物链环的修复。
Mol Cell Biol. 2005 Nov;25(21):9221-31. doi: 10.1128/MCB.25.21.9221-9231.2005.
6
Two PMS2 mutations in a Turcot syndrome family with small bowel cancers.一个患有小肠癌的Turcot综合征家族中的两个PMS2突变。
Am J Gastroenterol. 2005 Aug;100(8):1886-91. doi: 10.1111/j.1572-0241.2005.50441.x.
7
DNA mismatch repair.DNA错配修复
Annu Rev Biochem. 2005;74:681-710. doi: 10.1146/annurev.biochem.74.082803.133243.
8
Germline PMS2 mutations: one hit or two?生殖系PMS2突变：一击还是两击？
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9
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