Hess Martin T, Mendillo Marc L, Mazur Dan J, Kolodner Richard D
Department of Medicine, Cancer Center, Ludwig Institute for Cancer Research, University of California, San Diego School of Medicine, 9500 Gilman Drive, La Jolla, CA 92093-0669, USA.
Proc Natl Acad Sci U S A. 2006 Jan 17;103(3):558-63. doi: 10.1073/pnas.0510078103. Epub 2006 Jan 5.
Here, the ATP-binding, ATP hydrolysis, mispair-binding, sliding clamp formation, and Mlh1-Pms1 complex interaction properties of dominant mutant Msh2-Msh6 complexes have been characterized. The results demonstrate two mechanisms for dominance. In one, seen with the Msh6-S1036P and Msh6-G1067D mutant complexes, the mutant complex binds mispaired bases, is defective for ATP-induced sliding clamp formation and assembly of ternary complexes with Mlh1-Pms1, and occludes mispaired bases from other mismatch repair pathways. In the second, seen with the Msh6-G1142D complex, the mutant complex binds mispaired bases and is defective for ATP-induced sliding clamp formation but assembles ternary complexes with Mlh1-Pms1 that either occlude the mispaired base or prevent Mlh1-Pms1 from acting in alternate mismatch repair pathways.
在此，已对显性突变型Msh2-Msh6复合物的ATP结合、ATP水解、错配结合、滑动夹形成以及Mlh1-Pms1复合物相互作用特性进行了表征。结果证明了显性的两种机制。其一，在Msh6-S1036P和Msh6-G1067D突变复合物中可见，突变复合物结合错配碱基，在ATP诱导的滑动夹形成以及与Mlh1-Pms1形成三元复合物方面存在缺陷，并阻止其他错配修复途径接触错配碱基。其二，在Msh6-G1142D复合物中可见，突变复合物结合错配碱基，在ATP诱导的滑动夹形成方面存在缺陷，但与Mlh1-Pms1形成三元复合物，该复合物要么遮盖错配碱基，要么阻止Mlh1-Pms1在其他错配修复途径中发挥作用。
