Translesion synthesis articles from across Nature Portfolio

The authors perform a computational analysis of mutagenesis at non-B DNA structures formed by repetitive sequences. Having removed confounding factors, they present a landscape of mutagenesis different than previously thought, in which mechanisms such as the formation of abnormal secondary structures, polymerase slippage and occasional takeover by error-prone polymerases play an important role within, but not surrounding, the motifs.

MAD2L2 – as a member of the shieldin complex - counteracts resection during DNA repair. Here the authors demonstrate that MAD2L2 protects stalled replication forks from excessive resection, in a shieldin-independent and REV3L-dependent manner.

This manuscript elucidates new mechanisms of mutagenesis in mycobacteria by implicating two translesion DNA polymerases in genome diversification, including creating the mutations that underlie all antibiotic resistance in these global pathogens.

New data show that the HMCES protein suppresses DNA double-strand break formation by cross-linking to and thereby stabilizing an abasic site generated during replication-coupled repair of a DNA interstrand cross-link, thus demonstrating a physiological role of HMCES in DNA repair.

The structure of mismatched DNA-Polζ ternary complex provides a basis for understanding what makes Polζ adept at extending DNA synthesis past mismatched base pairs.

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.

The primase–polymerase PrimPol is required for bypassing G-quadruplexes in vertebrate cells by repriming replication downstream of the structures.

Deciphering the complexity of events at telomeres has enhanced understanding of how telomeres function to maintain genome integrity and how their dysfunction gives rise to human disease.

Telomerase is a nucleoprotein complex of a reverse transcriptase and an RNA that binds complementary telomeric-repeat DNA sequences and directs their extension. In this Commentary, the authors propose how hairpin structures formed by telomeric DNA repeats promote addition of telomerase repeats and why telomere sequences are evolutionarily conserved despite the problems that they pose to DNA replication.