engleski

Asynchronous replication of human subtelomeric regions

Replication of human genome is linked to different basic cellular processes. Studies conducted so far have shown that timing of DNA replication correlates with genomic instability, transcriptional activity, gene density and chromatin structure. Synchronous replication of alleles was demonstrated for genes with a biallelic expression while asynchronous replication for those with monoallelic mode of expression due to imprinting, X-inactivation or allelic exclusion. Little is known about replication timing(RT) of subtelomeric regions(SR), and its correlation with chromatin structure and function remains poorly understood. SRs of human chromosomes are highly unstable, rich in genes and frequently involved in aberrations and thus are of particular clinical interest. In this study the replication pattern of SR of chromosomes 2, 5, 7, 8, 9, 16, 19 and 20 was investigated using FISH method in lymphocytes of 8 healthy donors. At least 200 cells/probe/person were analyzed. The replication status of a locus was classified as unreplicated(s) and replicated(d). The analysis revealed marked heterogeneity of investigated SR. The data suggested a continuum of replication throughout S phase, with SR9p (dd:20.9±0.96%) being the first, and SR2p (dd:3.7±0.51%) the last to replicate (p<0.01). The results showed asynchronous replication at some SR. The frequency of sd ranged from 18.6% to 33.2% and the mean for SR19q2q16q20q5p (sd:31.08±0.52%) was significantly higher (p<0.01) compared to SR2p7q5q (sd:19.9±0.58%). This investigation revealed that different SR replicates at different times during S phase and that certain homologous loci replicate asynchronously. Although the significance of RT is unclear yet, it might contribute to the non-random involvement of specific SR in chromosomal rearrangements.

replication timing; subtelomeric region; human

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