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Título

Centromere-localized breaks indicate the generation of DNA damage by the mitotic spindle

AutorAlonso Guerrero, Astrid; Cano Gamero, Mercedes; Trachana, Varvara; Fütterer, Agnes; Pacios-Bras, Cristina; Panadero Díaz-Concha, Nuria; Cigudosa, Juan Cruz; Martínez-Alonso, Carlos; Van Wely, Karel H. M.
Palabras clavecentrosome
Chromosome Instability
Bouble-Strand Break
H2A.X
Fecha de publicación8-feb-2010
EditorNational Academy of Sciences (U.S.)
CitaciónPNAS. Proceedings of the National Academy of Sciences of the United States of America 107(9): 4159-4164 (2010)
SeriePNAS
0912143106
ResumenMost carcinomas present some form of chromosome instability in combination with spindle defects. Numerical instability is likely caused by spindle aberrations, but the origin of breaks and translocations remains elusive. To determine whether one mechanism can bring about both types of instability, we studied the relationship between DNA damage and spindle defects. Although lacking apparent repair defects, primary Dido mutant cells formed micronuclei containing damaged DNA. The presence of centromeres showed that micronuclei were caused by spindle defects, and cell cycle markers showed that DNA damage was generated during mitosis. Although the micronuclei themselves persisted, the DNA damage within was repaired during S and G2 phases. DNA breaks in Dido mutant cells regularly colocalized with centromeres, which were occasionally distorted. Comparable defects were found in APC mutant cell lines, an independent system for spindle defects. On the basis of these results, we propose a model for break formation in which spindle defects lead to centromere shearing.
Versión del editordoi:10.1073/pnas.0912143106
URIhttp://hdl.handle.net/10261/20884
ISSN1091-6490
Aparece en las colecciones: (CNB) Artículos
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