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- Title
BRIT1/MCPH1 Expression in Chronic Myeloid Leukemia and Its Regulation of the G2/M Checkpoint.
- Authors
Giallongo, C.; Tibullo, D.; La Cava, P.; Branca, A.; Parrinello, N.; Spina, P.; Stagno, F.; Conticello, C.; Chiarenza, A.; Vigneri, P.; Palumbo, G.A.; Di Raimondo, F.
- Abstract
BRIT1 (BRCT-repeat inhibitor of hTERT expression), also known as microcephalin (MCPH1), is a crucial gene in the complex cellular machine that is devoted to DNA repair and acts as a regulator of both the intra-S and G2/M checkpoints. The most important role of BRIT1/MCPH1 in the regulation of cell cycle progression appears to be the G2/M checkpoint. The K562 and peripheral blood cells of chronic myeloid leukemia (CML) patients at diagnosis were found to downregulate BRIT1/MCPH1. However, we could not find any correlation between bcr/abl activity and the BRIT1/MCPH1 level. In order to study the genomic instability of CML cells, we evaluated the ability of these cells to arrest mitotic division after exposure to hydroxyurea, a known genotoxic agent. We showed that CML cells continue to proliferate without the activation of the G2/M cell cycle checkpoint arrest or of the apoptotic mechanism. This behavior may predispose the cells to accumulate genomic defects. In conclusion, we found that CML cells have a low BRIT1/MCPH1 level and show a defective G2/M arrest, confirming that these cells have a constitutive genomic instability. Copyright © 2011 S. Karger AG, Basel
- Subjects
DNA repair; CELL cycle; BLOOD cells; CHRONIC myeloid leukemia; CHRONIC leukemia
- Publication
Acta Haematologica, 2011, Vol 126, Issue 4, p205
- ISSN
0001-5792
- Publication type
Article
- DOI
10.1159/000329911