Chromosomes lacking kinetochore proteins: their meta-anaphase location suggests potential malsegregation.

Abstract

We have previously reported that a rare chromosome may not carry the kinetochore protein complex--the CENtromere Proteins or CENPs. These chromosomes should not bind to spindle microtubules and, hence, should be found peripheral to the meta-anaphase arrangement exhibited by the chromosomes which do carry CENPs. This communication shows that this actually is the case. When 3T3 mouse cells were not treated with colcemid or hypotonic, the kinetochore-lacking (K-) as well as kinetochore-bearing (K+) chromosomes were found off the spindle zone. When the spindle is disrupted with mild hypotonic treatment or by colcemid, the frequency of K- chromosomes remains unchanged. However, even mild disruption of the spindle with hypotonic treatment increases the frequency of off-lying K+ chromosomes significantly. These data indicate that K- chromosomes do not bind to the spindle and, hence, are a factor in the genesis of aneuploidy. A considerable proportion of K- chromosomes carry the putative centromere DNA indicating that these are not acentric fragments. Since the CREST serum used recognizes all essential kinetochore proteins, the K- centromeres must also lack all essential CENPs.