The crystal structure of DNA mismatch repair protein MutS binding to a G x T mismatch

DNA mismatch repair ensures genomic integrity on DNA replication. Recognition of a DNA mismatch by a dimeric MutS protein initiates a cascade of reactions and results in repair of the newly synthesized strand; however, details of the molecular mechanism remain controversial. Here we present the crystal structure at 2.2 A of MutS from Escherichia coli bound to a G x T mismatch. The two MutS monomers have different conformations and form a heterodimer at the structural level. Only one monomer recognizes the mismatch specifically and has ADP bound. Mismatch recognition occurs by extensive minor groove interactions causing unusual base pairing and kinking of the DNA. Nonspecific major groove DNA-binding domains from both monomers embrace the DNA in a clamp-like structure. The interleaved nucleotide-binding sites are located far from the DNA. Mutations in human MutS alpha (MSH2/MSH6) that lead to hereditary predisposition for cancer, such as hereditary non-polyposis colorectal cancer, can be mapped to this crystal structure.     

上市公司经营活动状况对金融资产规模影响探究

越来越多的非金融业上市公司开始参与金融投资.通过实证研究来探索非金融业上市公司经营状况对其金融资产投资规模的影响,发现上市公司的金融资产有显著规模效应,同一行业内经营活动状况较好的上市公司有较少的金融投资,经营活动收入稳定增长的上市公司有较少的金融投资.