Genomic fingerprints of the world's soil ecosystems.

Despite the explosion of soil metagenomic data, we lack a synthesized understanding of patterns in the distribution and functions of soil microorganisms. These patterns are critical to predictions of soil microbiome responses to climate change and resulting feedbacks that regulate greenhouse gas release from soils. To address this gap, we assay 1,512 manually curated soil metagenomes using complementary annotation databases, read-based taxonomy, and machine learning to extract multidimensional genomic fingerprints of global soil microbiomes. Our objective is to uncover novel biogeographical patterns of soil microbiomes across environmental factors and ecological biomes with high molecular resolution. We reveal shifts in the potential for (i) microbial nutrient acquisition across pH gradients; (ii) stress-, transport-, and redox-based processes across changes in soil bulk density; and (iii) greenhouse gas emissions across biomes. We also use an unsupervised approach to reveal a collection of soils with distinct genomic signatures, characterized by coordinated changes in soil organic carbon, nitrogen, and cation exchange capacity and in bulk density and clay content that may ultimately reflect soil environments with high microbial activity. Genomic fingerprints for these soils highlight the importance of resource scavenging, plant-microbe interactions, fungi, and heterotrophic metabolisms. Across all analyses, we observed phylogenetic coherence in soil microbiomes-more closely related microorganisms tended to move congruently in response to soil factors. Collectively, the genomic fingerprints uncovered here present a basis for global patterns in the microbial mechanisms underlying soil biogeochemistry and help beget tractable microbial reaction networks for incorporation into process-based models of soil carbon and nutrient cycling.IMPORTANCEWe address a critical gap in our understanding of soil microorganisms and their functions, which have a profound impact on our environment. We analyzed 1,512 global soils with advanced analytics to create detailed genetic profiles (fingerprints) of soil microbiomes. Our work reveals novel patterns in how microorganisms are distributed across different soil environments. For instance, we discovered shifts in microbial potential to acquire nutrients in relation to soil acidity, as well as changes in stress responses and potential greenhouse gas emissions linked to soil structure. We also identified soils with putative high activity that had unique genomic characteristics surrounding resource acquisition, plant-microbe interactions, and fungal activity. Finally, we observed that closely related microorganisms tend to respond in similar ways to changes in their surroundings. Our work is a significant step toward comprehending the intricate world of soil microorganisms and its role in the global climate.

Perspectives From Students and Faculty on How Women Achieve Leadership Roles in Academic Medicine: An Exploratory Qualitative Study.

INTRODUCTION: The glass ceiling in academic medicine has resulted in lower pay and fewer career advancement opportunities for women. Creating change relies on preparing early-career women for positions of leadership, but most leadership programs focus on faculty, not trainees. The present exploratory qualitative study investigates how to prepare women medical students to be leaders in academic medicine. METHODS: Focus groups with medical students and faculty who identify as women were conducted at an academic medical center in the West. A total of 25 individuals (10 students and 15 faculty) participated. Recordings of focus groups were transcribed and coded using thematic analysis until saturation of themes was achieved. FINDINGS: Codes were organized into three themes: obstacles, support systems, and self-presentation. Obstacles identified included the subthemes microaggressions, macroaggressions, a lack of female role models in leadership, and personal characteristics such as the ability to self-promote and remain resilient. Support systems included sponsorship, allyship, mentorship, networking, and gender-specific role modeling subthemes. Self-presentation involved learning behaviors for demonstrating leadership and exuding confidence, being strategic about career moves, resiliency, and navigating social norms. CONCLUSIONS: The key themes of obstacles, support systems, and self-presentation are targets for systemic and individualistic improvement in leadership development.

Experimental Open Air Burning of Vegetation Enhances Organic Matter Chemical Heterogeneity Compared to Laboratory Burns.

Wildfires produce solid residuals that have unique chemical and physical properties compared to unburned materials, which influence their cycling and fate in the natural environment. Visual burn severity assessment is used to evaluate post-fire alterations to the landscape in field-based studies, yet muffle furnace methods are commonly used in laboratory studies to assess molecular scale alterations along a temperature continuum. Here, we examined solid and leachable organic matter characteristics from chars visually characterized as low burn severity that were created either on an open air burn table or from low-temperature muffle furnace burns. We assessed how the different combustion conditions influence solid and dissolved organic matter chemistries and explored the potential influence of these results on the environmental fate and reactivity. Notably, muffle furnace chars produced less leachable carbon and nitrogen than open air chars across land cover types. Organic matter produced from muffle furnace burns was more homogeneous than open air chars. This work highlights chemical heterogeneities that exist within a single burn severity category, potentially influencing our conceptual understanding of pyrogenic organic matter cycling in the natural environment, including transport and processing in watersheds. Therefore, we suggest that open air burn studies are needed to further advance our understanding of pyrogenic organic matter's environmental reactivity and fate.

Surgical Management of Vascular Malformations of the Upper Extremity: A 12-Year Retrospective Cohort Study.

INTRODUCTION: Vascular malformations (VMs) typically appear at birth and grow commensurately with patients. They can vary broadly in vessel type and tissue involvement, and upper extremity (UE) VMs can pose unique functional and aesthetic challenges in children. Given the advent of operative and nonoperative technologies like sclerotherapy and medications, a contemporary review of the surgical management of UE VMs is warranted. METHODS: We performed a retrospective review of all patients who had surgical management of VMs from 2010 to 2021 at The Children's Hospital of Philadelphia. Demographics, lesion characteristics, treatment (including preceding nonsurgical therapies), complications, and final outcomes were recorded. Operative notes were reviewed for date of operation, depth of excision, type of closure, and current procedural terminology code. RESULTS: Sixty-seven patients with 88 procedures were studied. Average patient age was 5.8 years, with 64% White and 67% male. Venous (34%) and lymphatic (19%) malformations were most common, and anatomic locations were most frequently on the hand (33%) and forearm (25%). The average lesion diameter was 4.2 cm, although this varied by location (eg, 2.9 cm, hand; 11.1 cm, chest wall). Fifty-eight patients (87%) underwent surgical excision as their index procedure, and 9 had sclerotherapy before surgery. Thirty-nine patients (60%) had subcutaneous excisions, and the remainder required subfascial or intramuscular excisions. Nearly all excisions were closed primarily (97%). Of the 53 patients with documented follow-up, 32 patients (60%) had complete resolution of their lesion as of their final visit. Thirty of these 32 patients with no clinical evidence of residual VM had only 1 surgery for excision. CONCLUSION: Upper extremity VMs were composed of diverse conditions with varying vessel types, size, depth, and anatomic sites. Surgical excision of VMs of the UE was safe and effective. A majority of VMs were fully excised after 1 procedure and frequently closed primarily with relatively low complication rates. Future work should investigate decision-making and outcomes of all treatment options of VMs of the UE for optimal functionality and aesthetics.

DNA strand breaks at centromeres: Friend or foe?

Centromeres are large structural regions in the genomic DNA, which are essential for accurately transmitting a complete set of chromosomes to daughter cells during cell division. In humans, centromeres consist of highly repetitive α-satellite DNA sequences and unique epigenetic components, forming large proteinaceous structures required for chromosome segregation. Despite their biological importance, there is a growing body of evidence for centromere breakage across the cell cycle, including periods of quiescence. In this review, we provide an up-to-date examination of the distinct centromere environments at different stages of the cell cycle, highlighting their plausible contribution to centromere breakage. Additionally, we explore the implications of these breaks on centromere function, both in terms of negative consequences and potential positive effects.

Clinical and operative risk factors for complications after Apert hand syndactyly reconstruction.

This study evaluated how Apert hand syndactyly presentations and reconstructive techniques influence reconstruction outcomes. All cases at a major paediatric hospital between 2007 and 2022 were analysed, including 98 web space reconstructions in 17 patients. Overall, 62% of hands developed complications and 15% required revision surgery. Upton hand type was significantly associated with postoperative complication incidence, specifically including range-of-motion deficits, flexion contracture, web creep and revision surgery. More severe syndactylies may benefit from additional measures to reduce complications. Rectangular commissural flaps showed 1.9 times greater complication risk than interdigitating triangular flaps, including 11.2 times greater risk of web creep. Zigzag volar finger flaps showed 1.8 times greater complication risk than straight-line incisions, including 3.8 times greater risk of web creep. Our study showed that interdigitating triangular commissural flaps and straight-line volar finger incisions are preferable to rectangular commissural and zigzag finger flaps in most cases of Apert hand syndactyly to minimize complications. LEVEL OF EVIDENCE: III.

Rethinking Aerobic Respiration in the Hyporheic Zone under Variation in Carbon and Nitrogen Stoichiometry.

Hyporheic zones (HZs)─zones of groundwater-surface water mixing─are hotspots for dissolved organic matter (DOM) and nutrient cycling that can disproportionately impact aquatic ecosystem functions. However, the mechanisms affecting DOM metabolism through space and time in HZs remain poorly understood. To resolve this gap, we investigate a recently proposed theory describing trade-offs between carbon (C) and nitrogen (N) limitations as a key regulator of HZ metabolism. We propose that throughout the extent of the HZ, a single process like aerobic respiration (AR) can be limited by both DOM thermodynamics and N content due to highly variable C/N ratios over short distances (centimeter scale). To investigate this theory, we used a large flume, continuous optode measurements of dissolved oxygen (DO), and spatially and temporally resolved molecular analysis of DOM. Carbon and N limitations were inferred from changes in the elemental stoichiometric ratio. We show sequential, depth-stratified relationships of DO with DOM thermodynamics and organic N that change across centimeter scales. In the shallow HZ with low C/N, DO was associated with the thermodynamics of DOM, while deeper in the HZ with higher C/N, DO was associated with inferred biochemical reactions involving organic N. Collectively, our results suggest that there are multiple competing processes that limit AR in the HZ. Resolving this spatiotemporal variation could improve predictions from mechanistic models, either via more highly resolved grid cells or by representing AR colimitation by DOM thermodynamics and organic N.

Wrist Level Tendon Repairs Utilizing a Novel Tendon Stapler Device: An Efficiency and Biomechanical Study.

BACKGROUND: A novel tendon stapler device (TSD) was recently developed and FDA-approved to improve the strength and consistency of primary tendon repairs. We hypothesized this TSD would demonstrate faster and superior biomechanical properties compared to a standard suture coaptation. We also hypothesized that the TSD biomechanical properties would be consistent across participants with differing tendon repair experience. METHODS: Participants included a novice, intermediate, and expert in tendon repairs. Timed comparisons were performed in flexor zones IV-V and extensor zones VI-VII on human cadaver arms. Suture repairs were performed with a modified Kessler with a horizontal mattress. TSD repairs were performed on the matched donor arms. Biomechanical testing included 2-mm gap force, ultimate failure load, and mode of failure. RESULTS: In total, 228 tendon coaptations from 12 donor arms were performed and analyzed. TSD coaptations were three times faster and withstood nearly 50% higher forces on the 2-mm gap testing and roughly 30% higher forces on ultimate failure testing. These findings did not change when the repair times were analyzed by individual participants. The suture coaptations failed from suture pull-through, suture breakage, and knot failure. The TSD coaptation failures only occurred from device pull-through. CONCLUSION: The TSD produces significantly faster and stronger primary tendon coaptations compared to a standard 4-strand core suture repair in human donor arms. These findings also demonstrated minimal variability among participants with differing tendon repair experience. Although further investigation is needed, this device has potential to revolutionize tendon repairs.

Influence of soil depth, irrigation, and plant genotype on the soil microbiome, metaphenome, and carbon chemistry.

IMPORTANCE: Carbon is cycled through the air, plants, and belowground environment. Understanding soil carbon cycling in deep soil profiles will be important to mitigate climate change. Soil carbon cycling is impacted by water, plants, and soil microorganisms, in addition to soil mineralogy. Measuring biotic and abiotic soil properties provides a perspective of how soil microorganisms interact with the surrounding chemical environment. This study emphasizes the importance of considering biotic interactions with inorganic and oxidizable soil carbon in addition to total organic carbon in carbonate-containing soils for better informing soil carbon management decisions.

Learning Curve of Wrist-level Tendon Repairs Using a Novel Tendon Stapler versus Traditional Suture Methods.

Numerous effective techniques for primary tendon coaptations exist. However, these techniques are complex and require a substantial amount of training to become proficient. Recently, a novel tendon stapler device (TSD) was developed that could potentially diminish the discrepancies among surgeons of varying levels of training. We hypothesized that the TSD would be easier to learn and would demonstrate improved learning curve efficiencies across participants of differing tendon repair experience compared with traditional suture methods. Participants included a novice, intermediate, and expert in tendon repairs. Comparisons were performed on wrist-level flexors and extensors from human donor arms. The suture repairs were performed with a modified Kessler with a horizontal mattress and were performed in one session on two donor arms by each participant. In a second session, each participant performed the TSD repairs on the matched, contralateral donor arms. Scatterplots fitted with Loess curves, one-way analysis of variance, Tukey pairwise comparisons, two-sided independent samples t test, and Fisher exact test were used to analyze findings. Results of our study showed that TSD repair times did not vary significantly by experience level. Suture repairs reached a stable "learned" level around repair #30, whereas the TSD repairs showed a more efficient curve that stabilized around repair #23. The TSD required less educational time, demonstrated a more efficient learning curve, and showed less variability across participants and repair order. Overall, the TSD is easy to adopt and may carry positive implications for surgeons and patients.

exo-FISH: Protocol for detecting DNA breaks in repetitive regions of mammalian genomes.

Detecting DNA breaks in defined regions of the genome is critical to advancing our understanding of genome stability maintenance. Here, we present exo-FISH, a protocol to label exposed single-stranded DNA in defined repetitive regions of mammalian genomes by combining in vitro restriction enzyme digestion on fixed cells with fluorescence in situ hybridization (FISH). We describe steps for cell harvesting and fixation, slide treatments, and FISH probe hybridization. We then detail procedures for imaging and analysis. For complete details on the use and execution of this protocol, please refer to Saayman et al. (2023).1.

Competing targets in English sibilant imitation.

This study investigates imitation of English /s/ to determine whether speakers converge toward normalized or raw acoustic targets. Participants exposed to increased spectral mean (SM) raised SM, converging toward both the raw acoustics of the model talker (who had high baseline SM) and the pattern of increased SM. However, after exposure to decreased SM, direction of shift depended on participant baseline. All participants converged to the raw acoustic values of the model talker, increasing or decreasing their own SM accordingly. These results suggest imitation is not necessarily mediated by perceptual normalization to different talkers, and raw acoustics can be the target of phonetic imitation. This has theoretical implications for the perception-production link and methodological implications for analysis of convergence studies.

ERCC6L2 mitigates replication stress and promotes centromere stability.

Structurally complex genomic regions, such as centromeres, are inherently difficult to duplicate. The mechanism behind centromere inheritance is not well understood, and one of the key questions relates to the reassembly of centromeric chromatin following DNA replication. Here, we define ERCC6L2 as a key regulator of this process. ERCC6L2 accumulates at centromeres and promotes deposition of core centromeric factors. Interestingly, ERCC6L2-/- cells show unrestrained replication of centromeric DNA, likely caused by the erosion of centromeric chromatin. Beyond centromeres, ERCC6L2 facilitates replication at genomic repeats and non-canonical DNA structures. Notably, ERCC6L2 interacts with the DNA-clamp PCNA through an atypical peptide, presented here in a co-crystal structure. Finally, ERCC6L2 also restricts DNA end resection, acting independently of the 53BP1-REV7-Shieldin complex. We propose a mechanistic model, which reconciles seemingly distinct functions of ERCC6L2 in DNA repair and DNA replication. These findings provide a molecular context for studies linking ERCC6L2 to human disease.

RAD51 Foci as a Biomarker Predictive of Platinum Chemotherapy Response in Ovarian Cancer.

PURPOSE: To determine the ability of RAD51 foci to predict platinum chemotherapy response in high-grade serous ovarian cancer (HGSOC) patient-derived samples. EXPERIMENTAL DESIGN: RAD51 and γH2AX nuclear foci were evaluated by immunofluorescence in HGSOC patient-derived cell lines (n = 5), organoids (n = 11), and formalin-fixed, paraffin-embedded tumor samples (discovery n = 31, validation n = 148). Samples were defined as RAD51-High if >10% of geminin-positive cells had ≥5 RAD51 foci. Associations between RAD51 scores, platinum chemotherapy response, and survival were evaluated. RESULTS: RAD51 scores correlated with in vitro response to platinum chemotherapy in established and primary ovarian cancer cell lines (Pearson r = 0.96, P = 0.01). Organoids from platinum-nonresponsive tumors had significantly higher RAD51 scores than those from platinum-responsive tumors (P < 0.001). In a discovery cohort, RAD51-Low tumors were more likely to have a pathologic complete response (RR, 5.28; P < 0.001) and to be platinum-sensitive (RR, ∞; P = 0.05). The RAD51 score was predictive of chemotherapy response score [AUC, 0.90; 95% confidence interval (CI), 0.78-1.0; P < 0.001). A novel automatic quantification system accurately reflected the manual assay (92%). In a validation cohort, RAD51-Low tumors were more likely to be platinum-sensitive (RR, ∞; P < 0.001) than RAD51-High tumors. Moreover, RAD51-Low status predicted platinum sensitivity with 100% positive predictive value and was associated with better progression-free (HR, 0.53; 95% CI, 0.33-0.85; P < 0.001) and overall survival (HR, 0.43; 95% CI, 0.25-0.75; P = 0.003) than RAD51-High status. CONCLUSIONS: RAD51 foci are a robust marker of platinum chemotherapy response and survival in ovarian cancer. The utility of RAD51 foci as a predictive biomarker for HGSOC should be tested in clinical trials.

An Evolution of the Surgical Management of Synpolydactyly: A Case Series of 21 Hands.

INTRODUCTION: Synpolydactyly is a rare congenital anomaly characterized by syndactyly and polydactyly in the central hand. Limited treatment guidelines exist for this complex condition. METHODS: A retrospective review of synpolydactyly patients was conducted at a large, tertiary pediatric referral center to describe our surgical experience and evolution of management. The Wall classification system was used to categorize cases. RESULTS: Eleven patients (21 hands) with synpolydactyly were identified. Most of the patients were White and had at least one first-degree relative who also had synpolydactyly. The Wall classification yielded the following results: 7 type 1A hands, 4 type 2B hands, 6 type 3 hands, and 4 uncategorizable hands. Each patient had an average of 2.6 surgeries and an average follow-up time of 5.2 years. The rates of postoperative angulation and flexion deformities were 24% and 38%, respectively, with many of these cases also demonstrating preoperative alignment abnormalities. These cases often required additional surgeries including osteotomies, capsulectomies, and/or soft tissue releases. The rate of web creep was 14% with 2 of these patients requiring revision surgery. Despite these findings, at the time of final follow-up, most patients had favorable functional outcomes, were able to engage in bimanual tasks, and were able to perform activities of daily living independently. CONCLUSIONS: Synpolydactyly is a rare congenital hand anomaly with a significant degree of variability in clinical presentation. The rates of angulation and flexion deformities as well as web creep are not insignificant. We have learned to prioritize correcting contractures, angulation deformities, and skin fusion, over simply trying to delete the "extra" number of bones as this may destabilize the digit(s).

Does Irreducibility Always Mean a Complex Dislocation? An Analysis of 33 Pediatric Metacarpophalangeal Joint Dislocations.

BACKGROUND: Previous failed reduction and certain radiographic indicators historically have been used to differentiate simple and complex metacarpophalangeal joint (MPJ) dislocations in children, the latter of which warrants open reduction. This investigation aimed to determine the necessity for open reduction with these indicators and establish a new treatment algorithm and educational focus for these rare injuries. METHODS: A 12-year retrospective study was conducted on all children with MPJ dislocations at a single pediatric hospital. The rates of successful closed reduction, number of reduction attempts, and radiographic findings were detailed. Operative details and postoperative outcomes were also gathered. RESULTS: Thirty-three patients with a mean age of 11.1 years were included. Most were male [ n = 27 (82%)] and had undergone two or more previous reduction attempts at an outside facility. Stable closed reduction was then achieved outside of the operating room in five patients and in the operating room under general anesthesia in another 14, for a total of 19 of 33 patients (57.6%). The thumb was injured most often [ n = 19 (57.6%)] and more likely to undergo successful closed reduction ( P = 0.04). There was no relationship between number of previous reduction attempts and ability to achieve closed reduction ( P = 0.72). Neither joint-space widening nor proximal phalanx bayonetting was correlated radiographically with failure of closed reduction ( P = 0.22 and P = 1, respectively). CONCLUSIONS: This study supports closed reduction of pediatric MPJ dislocations in the operating room under general anesthesia before conversion to open reduction, regardless of injury characteristics or previous reduction attempts. This strategy is likely to limit unnecessary open surgery and related risks. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, IV.

A New Source of Mutilating Hand Injuries: The Side-by-Side Utility Terrain Vehicle.

BACKGROUND: Rates of mutilating hand injuries are increasing from accidents caused by all-terrain vehicles (ATVs) and the recently popularized side-by-side utility terrain vehicles (UTVs). Increasing surgeon familiarity with upper extremity (UE) injury patterns, severity, and outcomes following ATV and UTV accidents may improve patient care and advocacy. METHODS: Retrospective comparisons of UE injury patterns, severity, hospital and intensive care unit (ICU) admission lengths, and number of operations were made between ATVs and UTVs. Findings were analyzed with Fisher exact tests, multivariate analysis of variance, analyses of variance with post hoc analyses, and multiple linear regressions. RESULTS: A total of 154 cases were identified for inclusion (ATV, n = 87; UTV, n = 67). Patient ages ranged from 4 to 89 years. The UTV group contained significantly more hand and finger injuries, and more of the fractures were open ( P = 0.005, P < 0.001, and P < 0.001, respectively). Riders of UTVs had nearly three times as many mutilating hand injuries and a nearly ninefold increase in amputations compared with ATV riders ( P < 0.001 and P < 0.001, respectively). On average, the UTV group spent 2.5 additional days in the hospital, 0.91 additional days in an ICU, and had 1.3 additional operations ( P = 0.001, P = 0.007, and P < 0.001, respectively). Vehicle type was the only variable significantly correlated with days in the hospital, ICU, and number of UE operations ( P = 0.002, P = 0.008, and P < 0.001, respectively). CONCLUSIONS: Hand surgeons are in a unique position to serve as forerunners for increasing public awareness of off-road vehicle risks and promoting rider safety. Collaborating with manufacturers and emergency care providers and directing teaching initiatives may improve patient outcomes. CLINICAL QUESTION/LEVEL OF EVIDENCE: Risk, II.

Implications of Soil Microbial Community Assembly for Ecosystem Restoration: Patterns, Process, and Potential.

While it is now widely accepted that microorganisms provide essential functions in restoration ecology, the nature of relationships between microbial community assembly and ecosystem recovery remains unclear. There has been a longstanding challenge to decipher whether microorganisms facilitate or simply follow ecosystem recovery, and evidence for each is mixed at best. We propose that understanding microbial community assembly processes is critical to understanding the role of microorganisms during ecosystem restoration and thus optimizing management strategies. We examine how the connection between environment, community structure, and function is fundamentally underpinned by the processes governing community assembly of these microbial communities. We review important factors to consider in evaluating microbial community structure in the context of ecosystem recovery as revealed in studies of microbial succession: (1) variation in community assembly processes, (2) linkages to ecosystem function, and (3) measurable microbial community attributes. We seek to empower restoration ecology with microbial assembly and successional understandings that can generate actionable insights and vital contexts for ecosystem restoration efforts.

Updating the probability of study success for combination therapies using related combination study data.

Combination therapies are becoming increasingly used in a range of therapeutic areas such as oncology and infectious diseases, providing potential benefits such as minimising drug resistance and toxicity. Sets of combination studies may be related, for example, if they have at least one treatment in common and are used in the same indication. In this setting, value can be gained by sharing information between related combination studies. We present a framework that allows the study success probabilities of a set of related combination therapies to be updated based on the outcome of a single combination study. This allows us to incorporate both direct and indirect data on a combination therapy in the decision-making process for future studies. We also provide a robustification that accounts for the fact that the prior assumptions on the correlation structure of the set of combination therapies may be incorrect. We show how this framework can be used in practice and highlight the use of the study success probabilities in the planning of clinical studies.

Centromeres as universal hotspots of DNA breakage, driving RAD51-mediated recombination during quiescence.

Centromeres are essential for chromosome segregation in most animals and plants yet are among the most rapidly evolving genome elements. The mechanisms underlying this paradoxical phenomenon remain enigmatic. Here, we report that human centromeres innately harbor a striking enrichment of DNA breaks within functionally active centromere regions. Establishing a single-cell imaging strategy that enables comparative assessment of DNA breaks at repetitive regions, we show that centromeric DNA breaks are induced not only during active cellular proliferation but also de novo during quiescence. Markedly, centromere DNA breaks in quiescent cells are resolved enzymatically by the evolutionarily conserved RAD51 recombinase, which in turn safeguards the specification of functional centromeres. This study highlights the innate fragility of centromeres, which may have been co-opted over time to reinforce centromere specification while driving rapid evolution. The findings also provide insights into how fragile centromeres are likely to contribute to human disease.