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DNA sequences contribute to the location and timing of replication origin firings. Here by allele-specific analysis, the authors show that replication asynchrony is associated with small cumulative variations in the initiation efficiency of origins, rather than with the activation of dormant origins.

The oncometabolite D-2-HG has been implicated in compromising DNA repair pathway. Here the authors show D-2-HG leads to genome-wide DNA hypermethylation and loss of CTCF coverage, which impairs the assembly of the homologous recombination DNA repair machinery and associated topology adjustment.

Dormant replication origins begin DNA synthesis under replication stress and are inactive in unperturbed cells. Here, the authors show that phospho-RecQL4 helicase blocks dormant origins’ activation by the Treslin/MTBP complex, facilitating its redistribution to activate dormant origins upon stress.

DNA double-strand breaks induce local genome maintenance and inhibition of replication initiation at nearby topologically associating domains without affecting global DNA synthesis.

Cohesin plays a crucial role in both chromosome organization and DNA repair. Here the authors find that cohesin mediated genome architecture prevents interactions between damaged chromatin. In contrast cohesin phosphorylation  appears to primarily impact DNA repair speed.

Spatial and temporal patterns of metazoan DNA replication are emerging as being dynamically regulated by tissue-specific and developmental cues, and by epigenetic modifications. These features might allow coordination with transcription and chromatin assembly, and enable changes in gene expression patterns.

LSH/HELLS is a chromatin remodeler promoting incorporation of histone variant macroH2A. Here the authors reveal a role for LSH in genome stability, in protecting nascent DNA at stalled forks mediated by macroH2A deposition and RAD51 filament formation.

The spindle assembly checkpoint (SAC) safeguards chromosome segregation by regulating the anaphase promoting complex/cyclosome (APC/C), allowing chromosomes to correctly attach to mitotic spindles. Here the authors reveal a role for Cullin–RING ubiquitin ligase complex 4 (CRL4) in regulating metaphase to anaphase transition via BUB3 degradation.

Tumor suppressor BRCA2 is known to stabilize and restart stalled DNA replication forks. Here the authors show that BRCA2 is recruited to the replication fork through its interaction with MCM10 and inhibits Primase-Polymerase-mediated repriming, lesion bypass and single strand DNA gap formation after DNA damage.

Several mechanisms are in place to ensure the accurate and timely replication of the genome as cells progress through S-phase. Here, the authors show that Mus81, an endonuclease involved in the response to DNA damage during replicative stress, also regulates the rate of DNA replication during normal growth.

DNA replication processes are often dysregulated in cancer. Here the authors analyse DNA synthesis patterns in cancer cells undergoing partial genome re-replication to reveal that re-replication exhibits aberrant replication fork dynamics and a skewed distribution of replication initiation that over-duplicates early-replicating genomic regions.

Origins of mammalian DNA replication are poorly characterised because they lack an Identifiable consensus sequence. Here the authors identify RepID, a protein that binds to a subset of G-rich replication origins and facilitates initiation from those origins.

RepID has previously been shown to promote origin firing. Here the authors reveal that RepID regulates replication origins via the recruitment of the CRL4 complex, and prevents re-initiation and unscheduled DNA replication.

Genome-wide mapping, mathematical models and functional genetic analyses suggest that distinct molecular interactions at replication initiation sites underlie the regulation of DNA replication in metazoans. In this Review, the authors discuss recent insights into these DNA–protein interactions, and the genetic and epigenetic features of mammalian replication origins.

A group of scientists in the systems biology community propose visual conventions for drawing biological diagrams.