DNA damage response and Immunity

Comparing to other biological systems, our understanding of plant extrachromosomal circular DNA (eccDNA) is limited. Here, the authors profile eccDNA from six rice tissues and investigate eccDNA characteristics, formation mechanisms, distribution, and functional implications.

TAK-931 is a selective CDC7 inhibitor and can induce replication stress (RS)-mediated chromosomal instability with antitumoral activity. Here the authors show that TAK-931-induced RS generates aneuploid cells with an inflammatory phenotype, rendering tumors sensitive to immune-checkpoint blockade.

Homologous recombination (HR) gene mutations are thought to be synthetic lethal with DNA polymerase theta (Polθ) inhibition. Here, the authors reveal that Polθ addiction is determined by the functional impact of gene mutations on DNA end resection activity.

GRB2 is known for its role in Receptor Tyrosine Kinase and RAS signaling. Here the authors unveil a GRB2 function and mechanism for DNA replication fork protection. GRB2 alleviates oncogenic replication stress, and in doing so, averts cancer immune destruction by inhibiting cGAS/STING and pro-inflammatory cytokine production.

The work suggests that DNA damage induced by either Cdk4 or Cdk6 knockout triggers anti-tumor immune responses through the STING-dependent type I interferon response.

CRISPR-Cas immunity systems safeguard prokaryotic genomes by inhibiting the invasion of mobile genetic elements. Here, the authors show that insertion sequences can efficiently insert into cas genes, thus inactivating CRISPR defenses and increasing bacterial susceptibility to foreign DNA invasion.

Polymerase (POL) θ inhibitors display synthetic lethality in tumours with homologous recombination repair deficiency. Here, the authors demonstrate that POLθ inhibition with novobiocin activates the cGAS/STING pathway in BRCA-deficient cancers.

DNA replication stress can result in genome instability. Here the authors show that the ubiquitin like modifier protein, ISG15, important during the innate immune response, acts at replication forks to mitigate DNA replication stress.

RnaseH2 is mutated in severe neuro-inflammatory disorder Aicardi‐Goutières syndrome. Here the authors reveal that RNase H2 controls cellular R-loop homeostasis to promote transcription, genome integrity and prevent R-loop-associated inflammation.

The cytidine deaminase APOBEC3A is a main source of mutagenesis in many types of cancer. Here the authors reveal that transient up-regulation of APOBEC3A and other pro-inflammatory genes can occur due to viral infection and genotoxic stress via multiple pathways.