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Publication : An anticlastogenic function for the Polycomb Group gene Bmi1.

First Author  Chagraoui J Year  2011
Journal  Proc Natl Acad Sci U S A Volume  108
Issue  13 Pages  5284-9
PubMed ID  21402923 Mgi Jnum  J:171236
Mgi Id  MGI:4949025 Doi  10.1073/pnas.1014263108
Citation  Chagraoui J, et al. (2011) An anticlastogenic function for the Polycomb Group gene Bmi1. Proc Natl Acad Sci U S A 108(13):5284-9
abstractText  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.
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