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EXO1 has a structural role to promote the MLH1-MLH3 nuclease complex to process meiotic recombination intermediates into crossovers. Here, the authors demonstrate that EXO1 function depends on conserved interactions with the MSH4 subunit of MSH4-MSH5, the MLH1 subunit of MLH1-MLH3, and DNA.

The MRX complex, required for double-strand break (DSB) repair by homologous recombination, has 3′ to 5′ exonuclease activity, but homologous recombination at a DSB uses a 3′-tailed molecule, which requires resection of the 5′ strand; here it is shown that in yeast, Sae2 nuclease promotes MRX to make an initial endonucleolytic cut on the 5′ strand that may allow MRX to digest the 5′ strand back to the end in a 3′ to 5′ fashion.

DNA in the cytoplasm can be a sign of abnormalities such as viral infections or cancer. A protein with a role in DNA-damage response was unexpectedly found to activate defences against the threats indicated by cytoplasmic DNA.

Tumor-associated neutrophils exhibit heterogeneity in breast cancer. Here, the authors identify a distinct precursor population (PreNeu) in estrogen receptor-positive tumors. PreNeu suppress homologous recombination in cancer cells, promoting error-prone DNA repair and enhancing sensitivity to PARP inhibitors.

BRCA1–BARD1 directly promotes double-strand break repair by stimulating long-range DNA end resection pathways.

Cas9 remains bound to DNA after cleavage and its removal is required for DNA double-strand break repair. Here, the authors show that the HLTF translocase disrupts the Cas9- DNA post-cleavage complexes in a process that requires the HLTF HIRAN domain and ATPase activity.

MCM8-9 and HROB function together in DNA damage response. Here, the authors describe the mechanism of DNA unwinding by MCM8-9 and its activation by HROB. HROB makes direct contacts with both MCM8 and MCM9 and promotes DNA unwinding downstream of MCM8-9 loading and hexameric ring formation on DNA.

Although millions of zeolite structures have been predicted, only about 200 have been prepared over the past six decades. An assembly–disassembly–organization–reassembly process has now enabled the synthesis of two zeolites previously thought to be unfeasible, which have high framework energy and rare structural features such as odd-membered rings.

The disassembly of a parent zeolite and its reassembly into two zeolites with targeted topologies is described. This process demonstrates that it is possible to target specific ring sizes in a zeolite by replacing one size of unit in the structure with alternative units of a different size.

The Mre11-Rad50 (MR) complex has key functions in the detection, signaling and repair of DNA breaks. Here the authors use transmission electron microscopy to show MR oligomerization is governed by a small beta-sheet protruding from the head domain of Rad50 at the base of the MR structure, and reveal MR head domain oligomerization is required for efficient DNA end resection.

Combinatorial CRISPRi screening was used to map genetic interactions in DNA damage response pathways, revealing known and new connections, including the roles of WDR48 and USP1 in preventing under-replication and SMARCAL1 and FANCM in remodelling persistent cruciform DNA structures.

Here the authors put forward a model in which the CtIP homolog Sae2 controls Mre11 endonuclease and 3’−5’ exonucleases via Rad50 by different mechanisms and reveals that the Mre11 endo-to-exonuclease switch is not required to process all blocked DNA ends

Clarke et al. identify chromatin factor ZNF280A, which is recruited to damaged chromatin where it promotes long-range DNA-end resection. Loss of ZNF280A is linked to genome instability in patients with 22q11.2 distal deletion syndrome.

An enzymatic ensemble including Dna2 functions in DNA end resection; the function of the single-stranded DNA binding protein RPA in this complex has been underappreciated. Here the authors employ molecular modeling, biochemistry, and single molecule biophysics to reveal RPA directly promotes Dna2 recruitment, nuclease and helicase activities.

Reconstitution of the activation of the MLH1–MLH3 endonuclease shows how crossovers are formed during meiosis.

It has previously been established that DNA end resection in yeast and in humans is under CDK control. Here the authors explain how phosphorylation regulates the capacity of Sae2 — the yeast orthologue of human CtIP — to promote DNA end resection.

DNA end resection is crucial for most DNA double-strand break repair pathways. This Review discusses the molecular mechanisms of end resection and its regulation, focusing on the roles of post-translational modifications throughout the cell cycle and in response to DNA damage.

Long non-coding RNAs transcribed at DNA damaged sites can play part in DNA damage response. Here the authors reveal that damaged induced lncRNAs can form DNA:RNA hybrids at resected DNA-ends. These hybrids are involved in recruiting HR-mediated repair machinery which, in turn, controls their level at DSBs.

A complex substrate containing mobile double Holliday junctions is now used to show that yeast proteins Sgs1 (DNA helicase) and Top3 (topoisomerase) act together to dissolve the junctions and avoid crossing over; the protein Rmi1 stimulates this process.

We have a limited understanding of how cells mark and identify newly replicated genomic loci that have a sister chromatid; here, unmethylated K20 in the tail of new histone H4 is shown to serve as a signature of post-replicative chromatin, which is specifically recognized by the homologous recombination complex TONSL–MMS22L.

Repair of broken DNA is vital for genome stability and to prevent the development of cancer. Research shows how the tumour-suppressor protein BRCA1 promotes a DNA-repair pathway called homologous recombination. See Article p.360

The repair of DNA double strand breaks is strictly controlled during the cell cycle by the CDK kinase. Here the authors identify the DDK kinase as a second major regulator for this cell cycle regulation and elucidate its functional targets.

Homologous recombination (HR) is an essential DNA repair pathway for genomic stability. Here the authors show that C17orf53/MCM8IP, an OB-fold containing protein, promotes HR through direct binding and activation of the MCM8-9 helicase complex.

Here, the authors show that replication protein A (RPA) tends to self-assemble into dynamic condensates, in a manner that is stimulated by ssDNA and regulated by RPA2 phosphorylation. RPA condensates are functionally important for telomere clustering and RAD52-dependent telomere maintenance.

Telomeres suppress the DNA damage response at chromosome ends. Here the authors show that in budding yeast the activity of the MRX complex in DNA repair and DNA damage signaling is inhibited by telomeric protein Rif2 via a short motif at the N-terminus.

In vitro and in vivo, the yeast Pif1 helicase is able to unwind four-stranded G-quadruplex (G4) DNA efficiently and suppress the genomic instability that occurs at such structures; these G4 maintenance activities are conserved among evolutionarily diverse Pif1 family helicases, including human PIF1, demonstrating the importance of this activity throughout evolution.

DNA replication stress drives genome instability and cancer. Here, Ölmezer and colleagues show that the helicase activity of multifunctional enzyme Dna2 suppresses dead-end replication structures that impair chromosome segregation if not removed by Holliday junction resolvase Yen1 in yeast.

Ranhja et al. find that budding yeast Dna2 is modified by sumoylation, and that sumoylation reduces the nuclease, but not helicase activity of Dna2 in vitro. In cells, expression of a Dna2 version that cannot be sumoylated leads to impaired DNA end resection and cell division.

The 'dissolvasome', composed of TopIIIα, BLM and RMI proteins, coordinates DNA-helicase and DNA-topoisomerase activities to resolve double Holliday junctions (dHJs) generated during DNA recombination and repair. The first crystal structure of a human TopIIIα–Rmi1 subcomplex provides insights into how topoisomerase is stimulated to promote dHJ decatenation.

When double-strand breaks occur in DNA, the broken ends must undergo processing to prepare them for repair. Here, and in an accompanying study, this processing reaction has now been replicated in vitro using yeast proteins. Processing minimally requires the activities of a helicase, a nuclease and a single-strand-binding protein, although the reaction is enhanced by the addition of three factors that help to target the core complex and stimulate the unwinding activity.

Mariotti et al. show that the iron-sulphur cluster in human DNA2 is required for its nuclease, helicase and ATPase activities. This study highlights the structural importance of the iron-sulphur cluster in human DNA2 and presents a separate redox-regulatory mechanism that controls DNA binding.