Publication Date:
2011-10-01
Description:
Various types of chromosomal aberrations, including numerical (aneuploidy) and structural (e.g., translocations, deletions), are commonly found in human tumors and are linked to tumorigenesis. Aneuploidy is a direct consequence of chromosome segregation errors in mitosis, whereas structural aberrations are caused by improperly repaired DNA breaks. Here, we demonstrate that chromosome segregation errors can also result in structural chromosome aberrations. Chromosomes that missegregate are frequently damaged during cytokinesis, triggering a DNA double-strand break response in the respective daughter cells involving ATM, Chk2, and p53. We show that these double-strand breaks can lead to unbalanced translocations in the daughter cells. Our data show that segregation errors can cause translocations and provide insights into the role of whole-chromosome instability in tumorigenesis.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Janssen, Aniek -- van der Burg, Marja -- Szuhai, Karoly -- Kops, Geert J P L -- Medema, Rene H -- 242617/European Research Council/International -- New York, N.Y. -- Science. 2011 Sep 30;333(6051):1895-8. doi: 10.1126/science.1210214.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Medical Oncology and Cancer Genomics Center, University Medical Center Utrecht, Universiteitsweg 100, 3584 CG, Utrecht, Netherlands.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/21960636" target="_blank"〉PubMed〈/a〉
Keywords:
Ataxia Telangiectasia Mutated Proteins
;
Cell Cycle Proteins/antagonists & inhibitors/metabolism
;
Cell Line
;
Cell Line, Tumor
;
Checkpoint Kinase 2
;
*Chromosomal Instability
;
*Chromosome Aberrations
;
*Chromosome Segregation
;
Cytokinesis
;
*DNA Breaks, Double-Stranded
;
DNA-Binding Proteins/metabolism
;
Histones/metabolism
;
Humans
;
Intracellular Signaling Peptides and Proteins/metabolism
;
Neoplasms/*genetics
;
Phosphorylation
;
Protein Kinase Inhibitors/pharmacology
;
Protein-Serine-Threonine Kinases/antagonists & inhibitors/metabolism
;
Protein-Tyrosine Kinases
;
Pyrimidines/pharmacology
;
Thiones/pharmacology
;
*Translocation, Genetic
;
Tumor Suppressor Protein p53/metabolism
;
Tumor Suppressor Proteins/metabolism
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
