The Genomic Architecture of Human DNA Replication Origins
Li, Z.; Yang, W.; Wu, G.; Yoshimura, S.; Mullighan, C. G.; Rosser, T. C.; Leslie-Clarkson, E. J.; Rabin, K. R.; Lupo, P. J.; Teachey, D. T.; Yang, J. J.
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The exact sites of DNA replication origins in human and other metazoans remain elusive. Examining human whole-genome sequencing data of 2,616 specimens, we observed conjoining reads at 2,025,756 non-random genomic positions, likely arising from nascent DNA and thus defining replication origins. These origins exhibited a 16 bp motif and periodic occurrence at the intervals of 10.5 bp and 200 bp. Genome-wide replication activity is related to the expression of DNA replication-related genes. Across the genome, DNA replication initiation is more active in early replicating regions, correlated with transcription activity in cis, enriched for de novo mutations and trait-associated polymorphisms. Our high-resolution mapping of human DNA replication origins points to molecular features that govern where and when replication begins in the genome.
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