Open AccessGenomic methods for measuring DNA replication dynamics
Author(s) -
Michelle L Hulke,
Dashiell J. Massey,
Am Koren
Publication year - 2019
Publication title -
chromosome research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.08
H-Index - 81
eISSN - 1573-6849
pISSN - 0967-3849
DOI - 10.1007/s10577-019-09624-y
Subject(s) - biology , dna replication , replication timing , genome instability , genetics , computational biology , chromatin , pre replication complex , eukaryotic dna replication , control of chromosome duplication , origin of replication , genome , origin recognition complex , gene , dna , dna damage
Genomic DNA replicates according to a defined temporal program in which early-replicating loci are associated with open chromatin, higher gene density, and increased gene expression levels, while late-replicating loci tend to be heterochromatic and show higher rates of genomic instability. The ability to measure DNA replication dynamics at genome scale has proven crucial for understanding the mechanisms and cellular consequences of DNA replication timing. Several methods, such as quantification of nucleotide analog incorporation and DNA copy number analyses, can accurately reconstruct the genomic replication timing profiles of various species and cell types. More recent developments have expanded the DNA replication genomic toolkit to assays that directly measure the activity of replication origins, while single-cell replication timing assays are beginning to reveal a new level of replication timing regulation. The combination of these methods, applied on a genomic scale and in multiple biological systems, promises to resolve many open questions and lead to a holistic understanding of how eukaryotic cells replicate their genomes accurately and efficiently.