RTEL1 helicase counteracts RAD51-mediated homologous recombination and fork reversal to safeguard replicating genomes.

Homologous recombination (HR) plays an essential role in the repair of DNA double-strand breaks (DSBs), replication stress responses, and genome maintenance. However, unregulated HR during replication can impair genome duplication and compromise genome stability. The mechanisms underlying HR regulation during DNA replication are obscure. Here, we find that RTEL1 helicase, RAD51, and RAD51 paralogs are enriched at stalled replication sites. The absence of RTEL1 leads to an increase in the RAD51-mediated HR and fork reversal during replication and affects genome-wide replication, which can be rescued by co-depleting RAD51 and RAD51 paralogs. Interestingly, co-depletion of fork remodelers such as SMARCAL1/ZRANB3/HLTF/FBH1 and expression of HR-defective RAD51 mutants also rescues replication defects in RTEL1-deficient cells. The anti-recombinase function of RTEL1 during replication depends on its interaction with PCNA and helicase activity. Together, our data identify the role of RTEL1 helicase in restricting RAD51-mediated fork reversal and HR activity to facilitate error-free genome duplication.

Compositional induced structural phase transitions in (1 - x)(K0.5Na0.5)NbO3-x(Ba0.5Sr0.5)TiO3 ferroelectric solid solutions.

Ferroelectric materials exhibiting switchable and spontaneous polarization have strong potential to be utilized in various novel electronic devices. Solid solutions of different perovskite structures induce the coexistence of various phases and enhance the physical functionalities around the phase coexistence region. The construction of phase diagrams is important as they describe the material properties, which are linked to the underpinning physics determining the system. Here we present the phase diagram of (K0.5Na0.5NbO3)-(Ba0.5Sr0.5TiO3) (KNN-BST) system as a function of composition and their associated physical properties. Lead-free (1 - x)KNN-xBST (0 ≤ x ≤ 0.3) solid solution ceramics were synthesized by conventional solid-state reaction technique. The X-ray diffraction and Raman spectroscopic studies indicate composition-dependent structural phase transitions from an orthorhombic phase for x = 0 to orthorhombic + tetragonal dual-phase (for 0.025 ≤ x ≤ 0.15), then a tetragonal + cubic dual-phase (x = 0.2) and finally a cubic single phase for x ≥ 0.25 at room temperature (RT). Among these, the orthorhombic + tetragonal dual-phase system shows an enhanced value of the dielectric constant at room temperature. The phase transition temperatures, orthorhombic to tetragonal (TO-T) and tetragonal to cubic (TC), decrease with the increase in BST concentrations. The ferroelectric studies show a decrease of both 2Pr and EC values with a rise in BST concentration and x = 0.025 showed a maximum piezoelectric coefficient.

RAD51 paralogs: Expanding roles in replication stress responses and repair.

Mammalian RAD51 paralogs are essential for cell survival and are critical for RAD51-mediated repair of DNA double-strand breaks (DSBs) by homologous recombination (HR). However, the molecular mechanism by which RAD51 paralogs participate in HR is largely unclear. Germline mutations in RAD51 paralogs are associated with breast and ovarian cancers and Fanconi anemia-like disorder, underscoring the crucial roles of RAD51 paralogs in genome maintenance and tumor suppression. Despite their discovery over three decades ago, the essential functions of RAD51 paralogs in cell survival and genome stability remain obscure. Recent studies unravel DSB repair independent functions of RAD51 paralogs in replication stress responses. Here, we highlight the recent findings that uncovered the novel functions of RAD51 paralogs in replication fork progression, its stability, and restart and discuss RAD51 paralogs as a potential therapeutic target for cancer treatment.