title: Evidence for involvement of HMGB1 protein in human DNA mismatch repair.
abstract: Defects in human DNA mismatch repair predispose to cancer, but many components of the pathway have not been identified. We report here the identification and characterization of a novel component required for mismatch repair in human cells. A 30-kDa protein was purified to homogeneity by virtue of its ability to complement a depleted HeLa extract in repair of mismatched heteroduplexes. The complementing activity was identified as HMGB1 (the high mobility group box 1 protein), a non-histone chromatin protein that facilitates protein-protein interactions and recognizes DNA damage. Evidence is also presented that HMGB1 physically interacts with MutSalpha and is required at a step prior to the excision of mispaired nucleotide in mismatch repair.
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536, USA.
authors.forename: Fenghua
authors.initials: F
authors.lastname: Yuan
authors.forename: Liya
authors.initials: L
authors.lastname: Gu
authors.forename: Shuangli
authors.initials: S
authors.lastname: Guo
authors.forename: Chunmei
authors.initials: C
authors.lastname: Wang
authors.forename: Guo-Min
authors.initials: GM
authors.lastname: Li
mesh_terms: D000595:Amino Acid Sequence; D020137:Base Pair Mismatch / Q000235:genetics*; D002467:Cell Nucleus / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism; D024742:HMG-Box Domains / Q000502:physiology; D024243:HMGB1 Protein / Q000737:chemistry / Q000378:metabolism*; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D000074081:MutS Homolog 3 Protein; D010446:Peptide Fragments; D013379:Substrate Specificity
chemical_list: D004268:DNA-Binding Proteins; D024243:HMGB1 Protein; C078444:MSH3 protein, human; D000074081:MutS Homolog 3 Protein; D010446:Peptide Fragments