DNA damage and repair articles within Nature

In Caenorhabditis elegans, paternal exposure to ionizing radiation results in HIS-24 and HPL-1-dependent genome instability phenotypes, causing embryonic lethality in the offspring.

Defective DNA interstrand crosslink repair in Fanconi anaemia drives extensive genomic rearrangements, thereby substantially increasing the risk of cancer development.

The nuclear mitotic apparatus protein NuMA helps to protect genes from oxidative damage by occupying regions around transcription start sites, binding DNA repair factors and promoting transcription following damage.

Structures of the ATP-hydrolysing RuvAB complex captured in multiple conformations provide mechanistic insights into coordinated ATPase and motor activity during DNA recombination.

DNA damage during chromothripsis is caused by deoxyinosine formation on accumulated RNA–DNA hybrids in micronuclei that are then recognized by N-methyl-purine DNA glycosylase and cleaved by apurinic/apyrimidinic endonuclease.

Analyses of single-cell whole-genome sequencing data show that somatic mutations are increased in the brain of individuals with Alzheimer’s disease compared to neurotypical individuals, with a pattern of genomic damage distinct from that of normal ageing.

Integrated structure–function studies show that transcription-coupled DNA repair (TCR)—rather than global genomic repair—is responsible for most chromosomal repair events in bacteria, and that TCR mainly occurs independently of the Mfd translocase.

Defective ribonucleotide excision repair causes ID4, an indel cancer signature characterized by deletions of 2–5 base pairs.

HELQ is differentially regulated by RAD51, which stimulates helicase activity, and RPA, which inhibits helicase activity and stimulates annealing.

Centromeres are able to recruit the homologous recombination machinery during G1 via CENP-A and HJURP, thereby preserving centromeric integrity even in the absence of a sister chromatid.

Endogenous formaldehyde accumulation reveals Cockayne syndrome in mice and stimulates production of the anorexiogenic peptide GDF15 in proximal tubule cells.

FAM72A differentially controls mutation rates by regulating uracil processing at different stages of the cell cycle, thereby regulating somatic hypermutation and class-switch recombination in B cells.

The authors resolve the structure of five complexes containing RNA polymerase II and the CSA and CSB proteins, offering insight into how the repair of DNA lesions is coupled to transcription.

Observations of rapid repair of double-stranded DNA breaks in sister choromosomes in Escherichia coli are consistent with a reduced-dimensionality-search model of RecA-mediated repair.

Structural and mechanistic data of the ADP-ribosyltransferase DarT demonstrate the role of ADP-ribosylation of DNA by this enzyme in generating toxicity and regulating cellular signalling processes in bacteria.

A tandem BRCT-domain-associated ubiquitin-dependent recruitment motif in BARD1 recruits BRCA1 to DNA double-strand breaks (DSBs) to promote homologous recombination and antagonize the 53BP1 DSB repair pathway that mediates non-homologous end joining.

The authors elucidate the mechanisms for the ubiquitylation specificity and recruitment of the ubiquitin ligase complex BRCA1–BARD1 to damaged DNA within chromatin to facilitate homologous recombination.

A small proportion of Spo11-dependent DNA double-strand breaks are ‘double cuts’—adjacent breaks that occur in concert—revealing that gap repair during meiosis includes that of DNA gaps generated by Spo11 itself.

RNA transcripts stimulate homologous recombination through the formation of DR-loops, intermediate structures that contain both DNA–DNA and DNA–RNA hybrids.

This Review examines the evidence showing that DNA damage is associated with ageing phenotypes, suggesting that it may have a central role as the cause of ageing.

Double-strand DNA break repair by the non-homologous end joining pathway involves the transition from a complex that bridges the DNA ends to a complex that aligns the DNA for ligation through the dissociation of the kinase subunits of the DNA-PK complexes.

DNA single-strand breaks in neurons accumulate at high levelsin functional enhancers.

Breaks in mitochondrial DNA cause leakage of mitochondrial RNA into the cytoplasm, enhancing immune surveillance and synergizing with nuclear DNA damage to mount a robust type-I interferon immune response.

During the repair of double-stranded DNA breaks, cohesin mediates the extrusion of loops of DNA along which phosphorylated H2AX spreads to establish a repair zone.

Single-stranded, DNA-damage-associated small RNAs generated by a BRCA1–RNA-interference complex promote PALB2–RAD52-mediated DNA repair at transcriptional termination pause sites that contain R-loops and are rich in single-stranded DNA breaks in both quiescent and proliferating cells.

A method of tracking break-induced replication reveals the details of this repair process and shows that it can be impaired by certain genomic elements and by transcription.

Depletion of TRF2—an essential mediator of telomere protection in most mammalian cells—in mouse embryonic stem cells activates a compensatory transcriptional program that renders TRF2 dispensable for their survival and proliferation.

In cells with microsatellite instability, expanded TA-dinucleotide repeats form cruciform structures that stall replication forks and cause chromosome shattering in the absence of the WRN helicase.

The PARP2–HPF1 histone-modifying complex bridges two nucleosomes to align broken DNA ends for ligation, initiating conformational changes that activate PARP2 and enable DNA damage repair.

Mutagenic lesions such as those that give rise to cancer frequently segregate—unrepaired—during cell division, resulting in phasing of multiple alleles across generations of daughter cells and consequent tumour heterogeneity.

Several mechanisms regulate the distribution of double-strand breaks during meiosis in Saccharomyces cerevisiae, ensuring that the shortest chromosomes are able to successfully recombine.

Cryo-EM structures of the FANCI–FANCD2 complex bound to DNA reveal that monoubiquitination triggers structural changes that enable the complex to function as a sliding DNA clamp and coordinate the repair of DNA interstrand crosslinks.

DNA interstrand crosslinks induced by acetaldehyde are repaired by both the Fanconi anaemia pathway and by a second, excision-independent repair mechanism.

The catalytic subunit of DNA-PK autophosphorylates and contributes to ribosome biogenesis and haematopoiesis by binding to the U3 small nucleolar RNA.

The structure of the multiprotein Fanconi anaemia core complex, determined using cryo-electron microscopy and mass spectrometry, shows that the complex adopts an extended asymmetric structure and highlights the structural and functional asymmetry of the RING finger domains.

Super-resolution microscopy demonstrates how changes in the 3D organization of chromatin protect DNA against excessive degradation following damage.

Cryo-electron microscopy structures reveal that the DNA-repair factor UV-DDB exposes inaccessible nucleosome lesions for binding by inducing a translational shift in the nucleosome position.

The E3 ubiquitin ligase TRAIP governs the choice between the NEIL3 or the Fanconi anaemia pathway for the repair of DNA interstrand crosslinks.

A deficiency of Dna2 causes duplication of DNA fragments and their insertion into the genome at double-stranded breaks in yeast.

The kinase CDK12 suppresses usage of intronic polyadenylation sites and thereby promotes the expression of genes involved in homologous recombination DNA repair.

DYNLL1 antagonizes end resection of DNA double-strand breaks, thereby inhibiting homologous repair, and the loss of DYNLL1 correlates with poor progression-free survival of patients with BRCA1-mutant ovarian cancer.

Differential DNA methylation and the long-range effects of chromatin organization lead to pronounced differences in recombination landscape between males and females.

The specificity of 53BP1 and its co-factors for particular DNA substrates during non-homologous end joining (NHEJ) derives from REV7–shieldin, a four-subunit DNA-binding complex that is required for REV7-dependent NHEJ but not for REV7-dependent DNA interstrand cross-link repair.

The 53BP1 effector complex shieldin is involved in non-homologous end-joining and immunoglobulin class switching, and acts to protect DNA ends to facilitate the repair of DNA by 53BP1.

53BP1 and shieldin recruit the CTC1–STN1–TEN1 complex and polymerase-α to sites of DNA damage to help control the repair of double-strand breaks.

Mutations in all three genes encoding ribonuclease H2 sensitize cells to poly(ADP–ribose) polymerase inhibitors by compromising ribonucleotide excision repair.

Polymerization of actin in the cell nucleus, promoted by the ARP2/3 complex, drives the clustering of double-strand DNA breaks into nuclear compartments where they can undergo homology-directed repair.

Relocalization of heterochromatic double-strand breaks to the nuclear periphery in Drosophila cells occurs via directed motions driven by nuclear actin filaments and myosins activated by the Smc5/6 complex.