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Chen et al. show that redox signals activate ADAR1 to fix faulty RNA pieces during DNA copying, ensuring smooth replication and protecting genome stability.

Regulated cell death and its dysregulation may contribute to chemoresistance. Here, the authors show that Ferroptosis Suppressor Protein 1 (FSP1) promotes chemoresistance in gastric cancer in part by suppressing ferroptosis.

Lactate fuels cancer growth by activating ERK signaling through GCN5-mediated lactylation of ERK, which disrupts ERK–MEK interactions. Development of a cell-penetrating peptide blocking lactylation slows KRAS-mutant tumor development.

KCTD10 interacts with the DNA replication machinery and the RNA polymerase complex, inducing ubiquitination and removal of the transcription machinery in the event of co-directional transcription–replication conflicts.

BRCA1 is a key regulator of DNA double-strand break repair, functioning to promote homologous recombination and repress non-homologous end-joining. Here the authors show that the ubiquitin ligase UHRF1 is recruited to breaks by BRCA1, where it targets RIF1 and thereby facilitates recombination.

Lou and colleagues describe the role of METTL16 in homologous recombination repair and demonstrate that PARP inhibition may be beneficial in the treatment of PDAC that is characterized by high METTL16.

BRCA1 dysfunction sensitizes cancer cells to PARP inhibitors (PARPi) but the underlying mechanism is unclear. Here, the authors identify RNF19A as a determinant of PARPi sensitivity, showing that RNF19A ubiquitinates BARD1, negatively regulates the BRCA1-BARD1 complex, and inhibits homologous recombination.

The RNA-sensing pathway has been associated with type I interferon (IFN) production induced by DNA damaging agents. Here the authors reveal that RIG-I, a cytosolic RNA sensor that recognizes RNA virus and initiates IFN signaling, is recruited to double-stranded breaks and suppresses non-homologous end joining.

AMPK and Parkin keep the necrosome in check. Lee et al. show that AMPK activates Parkin and prevents RIPK1−RIPK3 complex formation by promoting RIPK3 ubiquitination, thereby negatively regulating necroptosis, inflammation and tumour initiation.

Zhao et al. show that ASTE1 is a downstream effector of the shieldin complex, which cleaves the 3′ overhang of DNA double-strand breaks to promote shieldin-dependent non-homologous end-joining.

Ufmylation is a ubiquitylation-like protein modification but only a few ufmylation substrates and functions have been discovered so far. Here, the authors demonstrate ufmylation of histone H4 upon DNA damage and show that this modification is involved in the amplification of ATM activation.

The ATR pathway is active during DNA replication stress to maintain genome stability. Here the authors reveal the role of the zinc finger containing protein 161 (ZFP161) to facilitate replication fork stability by acting as a scaffold to facilitate the interaction between RPA and ATR/ATRIP.

C-terminal binding protein (CtBP) interacting protein (CtIP) is a fundamental factor for the initiation of DNA end resection to initiate DNA repair. Here the authors reveal mechanistic insights into the regulation of CtIP via the deubiquitinase USP52.

Overexpression of SNAIL confers tumour cells with cancer stem-like characteristics associated with tumour progression. Here the authors show that inhibition of CDK4/6 blocks tumour metastasis in triple negative breast cancer by targeting DUB3 which in turns deubiquitinates and stabilises SNAIL1.

Following double-strand break a cascade of events leads to the recruitment of repair factors to damaged sites. Here the authors identify ZNF506 as a key factor that mediates post-translational modification changes in H2AX affecting the DNA damage response.

Nowsheen et al. show that after DNA damage L3MBTL2 is recruited by MDC1 to DNA lesions where it is ubiquitylated by RNF8. Ubiquitylated L3MBTL2 then recruits RNF168 to promote DNA repair.

The bromodomain containing protein BRD9 has been reported to regulate chromatin remodeling and transcription. Here the authors reveal a role for BRD9 in homologous recombination by facilitating RAD51–RAD54 interaction.

Separation of intertwined sister chromatids, mediated by topoisomerase II, is essential for mitosis. In a separate mechanism, phosphorylation of topoisomerase II at Ser 1524 during the G2/M phase of the cell cycle recruits MDC1 to activate the decatenation checkpoint required for genomic stability.

Recruitment of 53BP1 to double-strand DNA breaks is an important step in the cellular response to DNA damage. Here, the histone methyltransferase MMSET is shown to be responsible for localized increases in a histone modification that is involved in recruiting 53BP1. The mechanism of MMSET recruitment to DNA damage sites is also investigated.

One of two papers that show that by inhibiting the deacetylase Sirt1, DBC1 promotes increased acetylation of p53 and p53-mediated apoptosis in human cells.

RAP80 helps to recruit BRCA1 to double-strand breaks, facilitating DNA damage responses. Here the authors report that phosphorylated USP13 deubiquitinates RAP80 after DNA damage, prompting recruitment to the break site.