Latereplicating

Latereplicating (late-replicating) refers to regions of the genome that are duplicated late during DNA synthesis in S phase. These regions are part of the genome's replication timing program, which assigns different genomic domains to replicate at distinct times during S phase.

Late-replicating domains tend to be gene-poor and enriched for repetitive elements and heterochromatin. They often coincide with lamin-associated domains at the nuclear envelope and carry repressive histone marks such as H3K9me3 and H3K27me3, reflecting a compact chromatin state and reduced transcriptional activity.

Replication timing is developmentally regulated and can vary between cell types and developmental stages. Large-scale changes in timing correlate with shifts in chromatin organization and 3D genome architecture, influencing the distribution and activation of replication origins in late domains.

Consequences of late replication include influences on mutation rates and genome stability, since late-replicating regions have less time for repair before cell division and are more prone to replication stress under stress conditions. Alterations in replication timing have been observed in cancer and developmental disorders.

Mapping latereplicating timing is accomplished with methods such as Repli-seq, which labels newly synthesized DNA in different S-phase windows to generate genome-wide timing profiles. Understanding latereplicating regions helps illuminate how chromatin state, transcription, and replication origin activity collaborate to shape genome organization.