title: Non-tumor cells from an MSH2-null individual show altered cell cycle effects post-UVB.
abstract: The multi-functionality of the DNA mismatch repair (MMR) proteins has been demonstrated by their role in regulation of the cell cycle and apoptosis, as well as DNA repair. Using a unique MSH2-/- non-tumor human lymphoblastoid cell line we show that MMR facilitates G2/M arrest after UVB-induced DNA damage. Deficiency in MSH2 leads to a decrease in the induction of G2/M cell cycle checkpoint following UVB radiation in MSH2-null non-tumor cells. We also show evidence that the above-mentioned cells deficient in MSH2 have decreased levels of key cell cycle proteins such as CHK1 phosphorylated at Ser345, CDC25C phosphorylated at Ser216 and CDC2 phosphorylated at Tyr15, Thr14, compared to MSH2-proficient cells after UVB radiation. In addition, we demonstrate an altered p53 protein in the MSH2-null cell line. Our data show that the MMR protein MSH2 is involved in the regulation of normal cell cycle response after UVB-induced DNA damage.
authors.affiliation: Department of Medical Genetics, University of Alberta, Alberta T6G 2H7, Canada.
authors.forename: Kelly A D
authors.initials: KA
authors.lastname: Narine
authors.forename: Kathleen E A
authors.initials: KE
authors.lastname: Felton
authors.forename: Arabesque A M
authors.initials: AA
authors.lastname: Parker
authors.forename: Victor A
authors.initials: VA
authors.lastname: Tron
authors.forename: Susan E
authors.initials: SE
authors.lastname: Andrew
mesh_terms: D002453:Cell Cycle / Q000235:genetics* / Q000528:radiation effects; D002455:Cell Division; D002460:Cell Line; D004249:DNA Damage / Q000528:radiation effects; D053843:DNA Mismatch Repair; D005434:Flow Cytometry; D016195:G2 Phase; D006801:Humans; D008214:Lymphocytes / Q000502:physiology; D051718:MutS Homolog 2 Protein / Q000172:deficiency*; D010766:Phosphorylation; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D016159:Tumor Suppressor Protein p53; C497172:MSH2 protein, human; D051718:MutS Homolog 2 Protein