Email updates

Keep up to date with the latest news and content from Cell Division and BioMed Central.

Open Access Open Badges Commentary

Merotelic attachments and non-homologous end joining are the basis of chromosomal instability

Astrid Alonso Guerrero, Carlos Martínez-A and Karel HM van Wely*

Author Affiliations

Department of Immunology and Oncology, Centro Nacional de Biotecnología/CSIC, Darwin 3, UAM Campus Cantoblanco, 28049 Madrid, Spain

For all author emails, please log on.

Cell Division 2010, 5:13  doi:10.1186/1747-1028-5-13

Published: 17 May 2010


Although the large majority of solid tumors show a combination of mitotic spindle defects and chromosomal instability, little is known about the mechanisms that govern the initial steps in tumorigenesis. The recent report of spindle-induced DNA damage provides evidence for a single mechanism responsible for the most prominent genetic defects in chromosomal instability. Spindle-induced DNA damage is brought about by uncorrected merotelic attachments, which cause kinetochore distortion, chromosome breakage at the centromere, and possible activation of DNA damage repair pathways. Although merotelic attachments are common early in mitosis, some escape detection by the kinetochore pathway. As a consequence, a proportion of merotelic attachments gives rise to chromosome breakage in normal cells and in carcinomas. An intrinsic chromosome segregation defect might thus form the basis of tumor initiation. We propose a hypothesis in which merotelic attachments and chromosome breakage establish a feedback loop that results in relaxation of the spindle checkpoint and suppression of anti-proliferative pathways, thereby promoting carcinogenesis.