DNA replication articles from across Nature Portfolio

Here the authors find that erythroblasts of myelodysplastic syndromes with SF3B1 mutation leading to inefficient erythropoiesis show DNA replication stress with accelerated forks and reduced R-loops. Restoring R-loops by a histone deacetylase inhibitor rescues erythroid differentiation.

Here the authors show that PARPi efficacy along with the fitness of BRCA1 deficient cells relies on FANCJ, which maintains S-phase PARP1 activity by preventing its sequestration with MSH2 on G-quadruplexes.

Poly(ADP-ribose) polymerase 1 (PARP1) functions together with TIMELESS and TIPIN to protect the replisome in early S phase from transcription–replication conflicts, and inhibiting PARP1 enzymatic activity may suffice for treatment efficacy in homologous recombination-deficient settings.

The DNA polymerase α–primase complex undergoes dramatic configurational rearrangements to synthesize chimeric RNA-DNA primers across two separate active sites while maintaining simultaneous interactions at opposite ends of the primer–template duplex.

Here, the authors characterise the zinc finger protein ZNF827 as a single stranded DNA binding protein that accumulates at stalled replication forks to activate the ATR-CHK1 pathway and engage homologous-recombination mediated DNA repair.

Bland et al. show that cancer types with heterozygous somatic hotspot mutations in the spliceosome component SF3B1 are vulnerable to PARP inhibition, which causes a defective response to replication stress.

Shi et al. show the role of myosin VI in the protection of stalled replication forks during replication stress.

A study on a yeast model explores how ssDNA gaps induce cell death and genomic instability, implicating Rad9 and Rad51 in gap repair and protection. Gaps forming secondary structures trigger chromosome fragility, deletions, rearrangements, or cell death pathways, showing how gaps are a vulnerability in cancer cells with opportunity for selective targeting.

The compact state of chromatin induced by the methylation of lysine 9 on histone H3 has long been implicated in a heritable state of transcriptional repression. A study now shows that transient deposition of H3K9me3 helps to stabilize stalled DNA replication forks, while its reversal enables accurate fork restart.

We determined the structure of the Polα–primase complex trapped in a DNA elongation state. Cryo-electron microscopy showed that primase has a role in facilitating the timely termination of primer DNA elongation by Polα by hanging on the primer–template complex.