DNA damage and repair articles from across Nature Portfolio

Combining genomics data from the TRACERx non-small-cell lung cancer (NSCLC) cohort and experimental data, we report that alterations in FAT1 are selected early during lung cancer evolution and cause chromosomal instability and whole-genome doubling.

Discovering molecular pathways that sensitize cells to poly(ADP-ribose) polymerase (PARP)- trapping inhibitors is important for anti-cancer therapy. Here, the authors report that inactivation of the CHD6 chromatin remodelling enzyme sensitizes cells to PARP inhibitors via reduced abasic site repair, PARP-1 accumulation on chromatin, and replication stress.

Whalen et al. report that increased DNA end resection in BRCA-deficient, PARP inhibitor-resistant cancers leads to increased sensitivity to DNA nicks, limiting tumor formation in mice, and propose the therapeutic exploration of nickases.

Telomeres are prone to oxidative damage, particularly the formation of the common lesion 8-oxoguanine. This study shows that the processing of 8-oxoguanine at telomeres by the DNA repair enzymes OGG1 and MUTYH glycosylases contributes to cellular senescence.

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.

Here the authors reveal that in addition to promoting class switch recombination via inhibition of DNA end processing, RIF1 fine-tunes the kinetics of plasma cell differentiation, thus providing an additional layer of control in the establishment of humoral immunity.

Combining genomics data from the TRACERx non-small-cell lung cancer (NSCLC) cohort and experimental data, we report that alterations in FAT1 are selected early during lung cancer evolution and cause chromosomal instability and whole-genome doubling.

Curiosity-driven and fundamental discovery science must be justified in its importance to human health and translational potential for practical applications and cures. However, many groundbreaking discoveries occur through the freedom to ask fundamental questions — the how and why — without knowing where they lead. Presented here is an example of a clinical target that emerged from a seemingly simple question in chromosome biology.