Stalled forks 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 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.

Ribonucleotides are incorporated into DNA during every S phase. Here, the authors show that replisome protein RTF2 localizes RNase H2 to the replisome, promoting ribonucleotide removal by RNase H2 when replication is ongoing but interfering with PRIM1-dependent restart following fork stalling.

Here the authors report that oncogenic c-Myc induces replication stress via increasing the amount of cohesins bound to chromatin at CTCF sites.

Replication stress represents a major threat to genome integrity of normal and cancer cells. Here, the authors find that the long non-coding RNA lncREST affects the replication stress response through interaction with nucleolin. This interaction bridges the recruitment of replication factors to stressed chromatin.

Recombination is essential for life. Here, the authors characterize FLIP as a novel regulator of the key recombination protein RAD51’s functions. FLIP loss caused marked sensitivity to DNA damage, increased DNA breakage and defective replication.

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.

The oncoprotein MYC undergoes multimerization to limit transcription–replication conflicts, thereby reducing the formation of DNA double-strand breaks in cancer cells.

DNA-dependent protein kinase catalytic subunit (DNA-PKcs) is important for replication-fork reversal under replication stress, and its inhibition can abolish PARP-inhibitor resistance in cancer cells.

The mechanisms by which translesion DNA polymerases mediate DNA repair are incompletely understood. A new study shows that Escherichia coli DNA polymerase IV is concentrated at the sites of arrested DNA synthesis by an interaction with SSB, the major single-stranded DNA-binding protein, specifically at stalled but not ongoing replication forks.

Poly(dA:dT) tracts characterize strong DNA replication origins in mammals and cause replication-fork collapse and DNA breaks that underlie the expression of fragile sites.

The mechanism underlying CCG-repeat expansions in patients with fragile X premutation is not well understood. Using a new experimental system in mammalian cells, a study in this issue reports that break-induced replication has a role in CGG-repeat instability.