Chronology and Pattern of Human Chromosome Replication

Abstract

The autoradiographic behavior of normal male and female chromosomes in blood leukocytes at various stages in the DNA synthesis period (S period) has been investigated with <sup>3</sup>H-thymidine. One X chromosome in female cells and the Y in male cells do not replicate their DNA or do so to a limited extent, 12 h before metaphase, when most of the other chromosomes are undergoing replication at a substantial rate. Asynchrony among the chromosomes is evident at that time. Furthermore, the X in female cells and the Y in male cells are the last chromosomes to finish their DNA replication. The replication of an elongated No. 1 autosome in a patient with primary amenorrhea has been compared to that of its normal homolog. The secondary constriction area, particularly prominent in the elongated No. 1, is the last area to finish replication in both the abnormal and normal No. 1 autosomes and is one of the latest segments in the human complement to finish replication. The leukocyte generation time was found to be 18 h or more in the presence of phytohemagglutinin (PHA). The data presented further delineate the time sequence and pattern of chromosomal replication in normal human leukocytes.