Two variants of MutS homolog hMSH5: prevalence in humans and effects on protein interaction.
MSH5 is known to play functional roles in an array of cellular processes such as DNA damage response and meiotic homologous recombination. Here, we report the characterization of an hMSH5 splicing variant (hMSH5sv) that resulted from the retention of the last 51 bp of hMSH5 intron 6, in which the encoded 17-amino acid insertion between codons 179 and 180 does not compromise its capability to interact with hMSH4. We have also identified an hMSH5 polymorphism (C85T) [corrected] that altered codon 29 of the hMSH5 gene resulting in a proline-to-serine change (P29S). The interaction domains of hMSH4 and hMSH5 have also been resolved. The P29S alteration is located within the interacting domain and leads to a weakened protein interaction with hMSH4. Together, our present study revealed the existence of two forms of hMSH5 variants in human cells. The different properties associated with these two hMSH5 variants underscore the potential functional diversity of the human hMSH5 gene.
Yi
Wei
W
School of Molecular Biosciences and Center for Reproductive Biology, Washington State University, Pullman 99164-4660, USA.
Wu
Xiling
X
Lee
Tai-Hsien
TH
Doggett
Norman A
NA
Her
Chengtao
C
D000595:Amino Acid Sequence; D001665:Binding Sites; D018797:Cell Cycle Proteins / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism*; D014644:Genetic Variation; D006801:Humans; D007668:Kidney / Q000378:metabolism*; D008969:Molecular Sequence Data; D009154:Mutation; D015995:Prevalence; D011485:Protein Binding; D025941:Protein Interaction Mapping / Q000379:methods*; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship
D018797:Cell Cycle Proteins; C409221:MSH4 protein, human; C118481:MSH5 protein, human