title: BRIT1/MCPH1 expression in chronic myeloid leukemia and its regulation of the G2/M checkpoint.
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.
authors.affiliation: Department of Clinical and Molecular Biomedicine, Section of Hematology, Ferrarotto Hospital, Via Citelli 6, Catania, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Giallongo
authors.forename: D
authors.initials: D
authors.lastname: Tibullo
authors.forename: P
authors.initials: P
authors.lastname: La Cava
authors.forename: A
authors.initials: A
authors.lastname: Branca
authors.forename: N
authors.initials: N
authors.lastname: Parrinello
authors.forename: P
authors.initials: P
authors.lastname: Spina
authors.forename: F
authors.initials: F
authors.lastname: Stagno
authors.forename: C
authors.initials: C
authors.lastname: Conticello
authors.forename: A
authors.initials: A
authors.lastname: Chiarenza
authors.forename: P
authors.initials: P
authors.lastname: Vigneri
authors.forename: G A
authors.initials: GA
authors.lastname: Palumbo
authors.forename: F
authors.initials: F
authors.lastname: Di Raimondo
mesh_terms: D000199:Actins / Q000037:antagonists & inhibitors; D000328:Adult; D000368:Aged; D018797:Cell Cycle Proteins; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D003571:Cytochalasin B / Q000633:toxicity; D048749:Cytokinesis / Q000187:drug effects; D003598:Cytoskeletal Proteins; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic; D042822:Genomic Instability; D006801:Humans; D006918:Hydroxyurea / Q000037:antagonists & inhibitors / Q000633:toxicity; D020014:K562 Cells; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000378:metabolism*; D007962:Leukocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009153:Mutagens / Q000633:toxicity; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D000199:Actins; D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C460645:MCPH1 protein, human; D009153:Mutagens; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D003571:Cytochalasin B; D006918:Hydroxyurea