Abstract

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.

中文翻译：

---

测量 DNA 复制动态的基因组方法。

 抽象的

基因组 DNA 根据定义的时间程序进行复制，其中早期复制基因座与开放染色质、更高的基因密度和增加的基因表达水平相关，而晚期复制基因座往往是异染色质的，并表现出更高的基因组不稳定率。事实证明，在基因组规模上测量 DNA 复制动态的能力对于理解 DNA 复制计时的机制和细胞后果至关重要。核苷酸类似物掺入定量和 DNA 拷贝数分析等多种方法可以准确重建各种物种和细胞类型的基因组复制时序图。最近的发展已将 DNA 复制基因组工具包扩展到直接测量复制起点活性的测定，而单细胞复制计时测定开始揭示复制计时调节的新水平。这些方法的结合，应用于基因组规模和多个生物系统，有望解决许多悬而未决的问题，并导致对真核细胞如何准确有效地复制其基因组的全面理解。