title: An anticlastogenic function for the Polycomb Group gene Bmi1.
abstract: BMI1 is a key component of multiprotein Polycomb repression complex 1 (PRC1), and its disruption in mice induces severe aplastic anemia by early adulthood. The contributing mechanisms responsible for this phenotype remain elusive. Here we show that transformed human cell lines as well as primitive hematopoietic cells exhibit a high frequency of spontaneous chromosome breaks upon BMI1 depletion and are hypersensitive to genotoxic agents. Consistent with these observations, we found that BMI1 is recruited rapidly to DNA damage foci where it blocks transcriptional elongation. We also show that BMI1 contributes to homologous recombination DNA repair and is required for checkpoint recovery. Taken together, our results suggest that BMI1 is critical for the maintenance of chromosome integrity in both normal and transformed cells.
authors.affiliation: Laboratory of Molecular Genetics of Hematopoietic Stem Cells, Institute for Research in Immunology and Cancer, Université de Montréal, Montréal, QC, Canada H3C 3J7.
authors.forename: Jalila
authors.initials: J
authors.lastname: Chagraoui
authors.forename: Josée
authors.initials: J
authors.lastname: Hébert
authors.forename: Simon
authors.initials: S
authors.lastname: Girard
authors.forename: Guy
authors.initials: G
authors.lastname: Sauvageau
mesh_terms: D000818:Animals; D002453:Cell Cycle / Q000502:physiology; D002460:Cell Line; D002875:Chromosomes / Q000378:metabolism; D004249:DNA Damage; D004260:DNA Repair; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology; D005786:Gene Expression Regulation; D006412:Hematopoietic Stem Cells / Q000166:cytology / Q000502:physiology; D006657:Histones / Q000235:genetics / Q000378:metabolism; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D063150:Polycomb Repressive Complex 1; D063146:Polycomb-Group Proteins; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D011995:Recombination, Genetic; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C489421:Bmi1 protein, mouse; D006657:Histones; D009687:Nuclear Proteins; D063146:Polycomb-Group Proteins; D011518:Proto-Oncogene Proteins; D012097:Repressor Proteins; C475961:gamma-H2AX protein, mouse; D063150:Polycomb Repressive Complex 1