PATTERNS OF DNA-REPLICATION OF HUMAN-CHROMOSOMES .2. REPLICATION MAP AND REPLICATION MODEL

Abstract

Combining higher resolution chromosome analysis and bromodeoxyuridine incorporation demonstrates that human chromosomes synthesize DNA in a segmental but highly coordinated fashion. Each chromosome replicates according to its innate pattern of chromosome structure (banding). R-positive bands are demonstrated as the initiation sites of DNA synthesis in all human chromosomes, including late-replicating chromosomes such as the LX and Y. Replication is clearly biphasic in the sense that late-replicating elements, such as G-bands, the Yh, C-bands and the entire LX, initiated replication after it was completed in the autosomal R-bands (euchromatin) with minimal or no overlap. The chronological priority of R-band replication followed by G-bands is also retained in the facultative heterochromatin or late-replicating X chromosome (LX). The inclusion of G-bands as a truly late-replicating chromatin type or G(Q)-heterochromatin is suggested. Lateral asymmetry (LA) in the Y chromosome can be detected after less than half-cycle in 5-bromodeoxyuridine, and the presence of at least 2 regions of LA in this chromosome is confirmed. The replicational map of human chromosomes is presented, and a model of replication chronology is suggested. Based on this model, a system of nomenclature is proposed to place individual mitoses (or chromosomes) within S-phase, according to their pattern of replication banding. Potential applications of this methodology in clinical and theoretical cytogenetics are suggested.