A mutation in the centriole-associated protein centrin causes genomic instability via increased chromosome loss in Chlamydomonas reinhardtii

Abstract

Background: The role of centrioles in mitotic spindle function remains unclear. One approach to investigate mitotic centriole function is to ask whether mutation of centriole-associated proteins can cause genomic instability.

Loss of centrioles causes chromosomal instability in vertebrate somatic cells

“…A relatively small increase in aneuploidy was reported upon loss of centrioles in fruit flies (3 vs. 1% in WT; Basto et al, 2006 ). Anastral spindle formation in centrin mutant Chlamydomonas reinhardtii produced a chromosome loss rate of 0.002 per chromosome per cell division ( Zamora and Marshall, 2005 ). Multiplying 0.002 by 34, the number of chromosomes in C. reinhardtii , suggests that chromosome loss may occur in ∼6% of cell divisions, which is close to our estimate of ∼10% in KO cells lacking centrioles.…”

Plk4 and Aurora A cooperate in the initiation of acentriolar spindle assembly in mammalian oocytes

“…However, spindle assembly can still occur after elimination of functional centrosomes in cultured cells ( Khodjakov et al, 2000 ; Mahoney et al, 2006 ) or the whole organism ( Megraw et al, 2001 ; Azimzadeh et al, 2012 ). Centrosomes do, however, enhance mitotic fidelity ( Delattre and Gönczy, 2004 ; Zamora and Marshall, 2005 ; McCoy et al, 2015 ). Nevertheless, in most metazoans, centrioles are naturally eliminated during oogenesis before female meiosis ( Delattre and Gönczy, 2004 ) Thus, high fidelity of chromosome transmission during meiosis I in the oocyte, essential to correctly establish the next generation, relies on acentrosomal spindle assembly ( Heald et al, 1996 ).…”

The centrosome and bipolar spindle assembly

“…Fully functional spindles can form in their absence, although there can be other mitotic and cytokinetic defects in spindles lacking functional centrosomes. [57][58][59] Taken together, the results of experimental manipulation, which rid cells of their resident centrosomes, as well as observations in cells that never had centrosomes in the first place has supported the notion that centrosomes do not actually play a role in building a normal mitotic spindle. Rather, a contemporary view suggests these organelles are merely passengers "brought along for the ride," with their major role being to template the onset of mitosis results in the release of the MTs into the mitotic cytoplasm.…”