Premium
Spindles losing their bearings: Does disruption of orientation in stem cells predict the onset of cancer?
Author(s) -
Graham Trevor A.,
Jawad Noor,
Wright Nicholas A.
Publication year - 2010
Publication title -
bioessays
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.175
H-Index - 184
eISSN - 1521-1878
pISSN - 0265-9247
DOI - 10.1002/bies.201000032
Subject(s) - biology , stem cell , somatic cell , mitosis , cell division , sister chromatids , chromosome instability , crypt , microbiology and biotechnology , spindle apparatus , genome instability , genetics , mutation , asymmetric cell division , cell , dna , gene , chromosome , dna damage , endocrinology
Recently, Quyn et al . demonstrated that cells within the stem cell zone of human and mouse intestinal crypts tend to align their mitotic spindles perpendicular to the basal membrane of the crypt. This is associated with asymmetric division, whereby particular proteins and individual chromatids are preferentially segregated to one daughter cell. In colonic mucosa containing a heterozygous adenomatous polyposis coli gene ( APC ) mutation the asymmetry is lost. Here, we discuss asymmetric stem cell division as an anti‐tumourigenic mechanism. We describe how hierarchical tissue structures suppress somatic evolution, and discuss the relative merits of template strand retention to limit the accumulation of DNA replication errors. We suggest experiments to determine whether somatic mutations resulting in loss of spindle alignment confer an advantage within the stem cell niche. Finally, we discuss whether lack of spindle alignment constitutes an oncogenic event per se , with particular reference to studies in model organisms, and the timing of chromosomal instability in human cancers.