Evidence for involvement of HMGB1 protein in human DNA mismatch repair.
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.
Yuan
Fenghua
F
Department of Pathology and Laboratory Medicine, University of Kentucky Medical Center, 800 Rose Street, Lexington, KY 40536, USA.
Gu
Liya
L
Guo
Shuangli
S
Wang
Chunmei
C
Li
Guo-Min
GM
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
D004268:DNA-Binding Proteins; D024243:HMGB1 Protein; C078444:MSH3 protein, human; D000074081:MutS Homolog 3 Protein; D010446:Peptide Fragments