Nucleotide excision repair articles from across Nature Portfolio

DNA damage stalls RNA polymerase II and halts gene expression. Here, the authors reveal how cells clear stalled polymerase by two hierarchical pathways, in which CSB/CRL4^CSA -triggered ubiquitylation enables rapid TFIIH-driven removal, and with VCP-mediated extraction acting as a backup when this fails.

DNA damage can arise from natural cellular processes, but how cells prevent resulting mutations is unclear. Here, the authors show that the enzyme Polκ protects mouse tissues from mutations caused by endogenous guanine lesions, revealing how DNA repair and damage tolerance pathways cooperate to maintain genome integrity.

The UvrA protein is a DNA damage sensor in the bacterial nucleotide excision repair pathway. Here, the authors present a series of cryo-EM structures representing snapshots of UvrA’s ATP-dependent detection of DNA damage.

This computational modelling study unveils the detailed DNA translocation mechanisms of two archetypal SF2 family helicases, XPD and DinG, and sheds light on the functional impact of XPD-associated mutations on genetic disease etiology.

DNA damage repair is in the spotlight this year — the Nobel Prize in Chemistry 2015 was awarded to Tomas Lindahl, Paul Modrich and Aziz Sancar “for mechanistic studies of DNA repair”.