Cell cycle and centromere FISH studies in premature centromere division.
BACKGROUND
Mitotic configurations consistent in split centromeres and splayed chromatids in all or most of the chromosomes or premature centromere division (PCD) have been described in three categories. (1) Low frequency of PCD observed in colchicines-treated lymphocyte cultures from normal individuals. (2) High frequency of PCD with mosaic variegated aneuploidy. (3) High frequency of PCD as a sole chromosome abnormality observed in individuals with no recognizable clinical pattern. We report four members of a family with the third category of PCD.


METHODS
Cell cycle duration assessed by average generation time using differential sister chromatid stain analysis and FISH studies of DNA centromere sequences in PCD individuals, are included and compared with previously reported PCD individuals from 9 families.


RESULTS
We observed PCD in colchicine-treated cultures from the propositus, his father, and two paternal aunts but not in his mother and four other paternal and maternal family members, as well as in untreated cultures from the propositus and his father. We observed cytological evidence of active centromeres by Cd stain. Significative cell cycle time reduction in anaphases of PCD individuals (average generation time of 21.8 h;SD 0.4) with respect to individuals without PCD (average generation time of 31.8 h;SD 3.9) was observed (P < 0.005, Student t-test for independent samples). Increased cell proliferation kinetics was observed in anaphasic cells of individuals with PCD, by differential sister chromatid stain analysis. FISH studies revealed the presence of alpha satellite DNA from chromosomes 1, 13, 21/18, X, all centromeres, and CENP-B box sequences in metaphasic and anaphasic cells from PCD individuals.


CONCLUSIONS
This report examines evidences of a functional relationship between PCD and cell cycle impairment. It seems that essential centromere integrity is present in these cases.
Corona-Rivera
Alfredo
A
Instituto de Genética Humana Dr, Enrique Corona Rivera, Departamento de Fisiología, Centro Universitario Ciencias de la Salud, Universidad de Guadalajara, Guadalajara, Jalisco, México. alcorona@cucs.udg.mx
Salamanca-Gomez
Fabio
F
Bobadilla-Morales
Lucina
L
Corona-Rivera
Jorge R
JR
Palomino-Cueva
Cesar
C
Garcia-Cobian
Teresa A
TA
Corona-Rivera
Enrique
E
D000328:Adult; D002453:Cell Cycle / Q000235:genetics*; D002503:Centromere / Q000737:chemistry / Q000648:ultrastructure*; D002648:Child; D002869:Chromosome Aberrations; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007621:Karyotyping; D008297:Male; D010375:Pedigree