Mycorrhizal Types Regulate Tree Spatial Associations in Temperate Forests: Ectomycorrhizal Trees Might Favour Species Coexistence.

In temperate mixed forests, dominant ectomycorrhizal (EM) tree species usually coexist with diverse arbuscular mycorrhizal (AM) understorey tree species. Here, we investigated the spatial associations between AM and EM trees in two > 20 ha temperate forest mega-plots to better understand the observed 'EM-dominant versus AM-diverse' coexistence. Overall, we found that positive spatial associations (e.g., facilitation) were mostly related to EM trees, while negative spatial associations (e.g., inhibition) were mainly related to AM trees. Because adult EM trees tended to facilitate surrounding AM and EM saplings and other EM adults in these two forests, facilitation hotspots that stabilize AM-EM tree coexistence should be centred around EM tree species rather than around AM tree species. Together, we propose a novel EM-stabilization mechanism, which emphasises how, despite some species-specific variation, EM tree species foster 'EM-dominant versus AM-diverse' coexistence in temperate mixed forests by facilitating other trees.

Host specificity of plant-associated bacteria is negatively associated with genome size and host abundance along a latitudinal gradient.

Host specialization plays a critical role in the ecology and evolution of plant-microbe symbiosis. Theory predicts that host specialization is associated with microbial genome streamlining and is influenced by the abundance of host species, both of which can vary across latitudes, leading to a latitudinal gradient in host specificity. Here, we quantified the host specificity and composition of plant-bacteria symbioses on leaves across 329 tree species spanning a latitudinal gradient. Our analysis revealed a predominance of host-specialized leaf bacteria. The degree of host specificity was negatively correlated with bacterial genome size and the local abundance of host plants. Additionally, we found an increased host specificity at lower latitudes, aligning with the high prevalence of small bacterial genomes and rare host species in the tropics. These findings underscore the importance of genome streamlining and host abundance in the evolution of host specificity in plant-associated bacteria along the latitudinal gradient.

A Pillar[5]arene-Containing Metal-Organic Framework for Rapid and Highly Capable Adsorption of a Mustard Gas Simulant.

Mustard gas causes irreversible damage upon inhalation or contact with the human body. Consequently, the development of adsorbents for effective interception of mustard gas at low concentrations and high flow rates is an urgent necessity. Here we report a stable porous pillar[5]arene-containing metal-organic framework (MOF) based on zirconium (EtP5-Zr-scu), demonstrating that embedding pillar[5]arene units in MOFs can provide specific binding sites for efficient adsorption of a mustard gas simulant, 2-chloroethyl ethyl sulfide (CEES). EtP5-Zr-scu achieves a higher capacity and more rapid adsorption compared to its counterpart without embedded pillar[5]arene units (H4tcpt-Zr-scu) and perethylated pillar[5]arene (EtP5) alone. Single crystal X-ray diffraction and solid-state nuclear magnetic resonance reveal that the enhanced performance of EtP5-Zr-scu is derived from the host-guest complexation between CEES and pillar[5]arene moieties. Moreover, breakthrough experiments confirmed that the interception performance of EtP5-Zr-scu against CEES (800 ppm, 120 mL/min) was significantly improved (566 min/g) compared with H4tcpt-Zr-scu (353 min/g) and EtP5 (0.873 min/g), attributed to the integration of open channels with specific recognition sites. This work marks a significant advancement in the development of macrocycle-incorporated crystalline framework materials with recognition sites for the efficient capture of guest molecules.

CircLIFRSA/miR-1305/PTEN axis attenuates malignant cellular processes in non-small cell lung cancer by regulating AKT phosphorylation.

BACKGROUND: Non-small cell lung cancer (NSCLC) is typically diagnosed at advanced stages, which limits the effectiveness of therapeutic interventions. The present study aimed to explore the role of the newly identified circLIFRSA in the PTEN/AKT signaling pathway and its involvement in the malignant processes of NSCLC. METHODS: CircLIFRSA expression was identified through microarray analysis, and its levels in NSCLC samples were quantified by RT-qPCR. The impact of circLIFRSA on cell growth, proliferation, apoptosis, and cell cycle were evaluated by MTT assay, colony formation assay, and flow cytometry. Additionally, Western blotting was employed to analyze the expression of PTEN and phosphorylated AKT (pAKT) in NSCLC cells. RESULTS: The expression of circLIFRSA was found to be significantly reduced in NSCLC cells and tissues. This downregulation correlated with various clinicopathological characteristics and indicated its potential as an early diagnostic biomarker for NSCLC. Importantly, circLIFRSA was shown to inhibit cell growth and proliferation while promoting apoptosis in NSCLC cells. Mechanically, circLIFRSA was found to attenuate the malignant processes of NSCLC cells via the miR-1305/PTEN axis and the suppression of AKT phosphorylation. CONCLUSIONS: These findings indicate that circLIFRSA/miR-1305/PTEN axis attenuates malignant processes by regulating AKT phosphorylation, and provide new insights into the potential of circLIFRSA as a biomarker for early diagnosis and as a promising therapeutic target in NSCLC.

Bone-derived PDGF-BB enhances hippocampal non-specific transcytosis through microglia-endothelial crosstalk in HFD-induced metabolic syndrome.

BACKGROUND: It is well known that high-fat diet (HFD)-induced metabolic syndrome plays a crucial role in cognitive decline and brain-blood barrier (BBB) breakdown. However, whether the bone-brain axis participates in this pathological process remains unknown. Here, we report that platelet-derived growth factor-BB (PDGF-BB) secretion by preosteoclasts in the bone accelerates neuroinflammation. The expression of alkaline phosphatase (ALPL), a nonspecific transcytosis marker, was upregulated during HFD challenge. MAIN BODY: Preosteoclast-specific Pdgfb transgenic mice with high PDGF-BB concentrations in the circulation recapitulated the HFD-induced neuroinflammation and transcytosis shift. Preosteoclast-specific Pdgfb knockout mice were partially rescued from hippocampal neuroinflammation and transcytosis shifts in HFD-challenged mice. HFD-induced PDGF-BB elevation aggravated microglia-associated neuroinflammation and interleukin-1ß (IL-1ß) secretion, which increased ALPL expression and transcytosis shift through enhancing protein 1 (SP1) translocation in endothelial cells. CONCLUSION: Our findings confirm the role of bone-secreted PDGF-BB in neuroinflammation and the transcytosis shift in the hippocampal region during HFD challenge and identify a novel mechanism of microglia-endothelial crosstalk in HFD-induced metabolic syndrome.

A cell wall-localized ß-1,3-glucanase promotes fiber cell elongation and secondary cell wall deposition.

ß-1,3-glucanase functions in plant physiological and developmental processes. However, how ß-1,3-glucanase participates in cell wall development remains largely unknown. Here, we answered this question by examining the role of GhGLU18, a ß-1,3-glucanase, in cotton (Gossypium hirsutum) fibers, in which the content of ß-1,3-glucan changes dynamically from 10% of the cell wall mass at the onset of secondary wall deposition to <1% at maturation. GhGLU18 was specifically expressed in cotton fiber with higher expression in late fiber elongation and secondary cell wall (SCW) synthesis stages. GhGLU18 largely localized to the cell wall and was able to hydrolyze ß-1,3-glucan in vitro. Overexpression of GhGLU18 promoted polysaccharide accumulation, cell wall reconstruction, and cellulose synthesis, which led to increased fiber length and strength with thicker cell walls and shorter pitch of the fiber helix. However, GhGLU18-suppressed cotton resulted in opposite phenotypes. Additionally, GhGLU18 was directly activated by GhFSN1 (fiber SCW-related NAC1), a NAC transcription factor reported previously as the master regulator in SCW formation during fiber development. Our results demonstrate that cell wall-localized GhGLU18 promotes fiber elongation and SCW thickening by degrading callose and enhancing polysaccharide metabolism and cell wall synthesis.

Disturbance history, neighborhood crowding and soil conditions jointly shape tree growth in temperate forests.

Understanding how different mechanisms act and interact in shaping communities and ecosystems is essential to better predict their future with global change. Disturbance legacy, abiotic conditions, and biotic interactions can simultaneously influence tree growth, but it remains unclear what are their relative contributions and whether they have additive or interactive effects. We examined the separate and joint effects of disturbance intensity, soil conditions, and neighborhood crowding on tree growth in 10 temperate forests in northeast China. We found that disturbance was the strongest driver of tree growth, followed by neighbors and soil. Specifically, trees grew slower with decreasing initial disturbance intensity, but with increasing neighborhood crowding, soil pH and soil total phosphorus. Interestingly, the decrease in tree growth with increasing soil pH and soil phosphorus was steeper with high initial disturbance intensity. Testing the role of species traits, we showed that fast-growing species exhibited greater maximum tree size, but lower wood density and specific leaf area. Species with lower wood density grew faster with increasing initial disturbance intensity, while species with higher specific leaf area suffered less from neighbors in areas with high initial disturbance intensity. Our study suggests that accounting for both individual and interactive effects of multiple drivers is crucial to better predict forest dynamics.

The Impact of 90 Parkinson's Disease-Risk Single Nucleotide Polymorphisms on Urinary Bis(monoacylglycerol)phosphate Levels in the Prodromal and PD Cohorts.

Parkinson's disease (PD) is a common neurodegenerative disorder with a prolonged prodromal phase. Higher urinary bis(monoacylglycerol)phosphate (BMP) levels associate with LRRK2 (leucine-rich repeat kinase 2) and GBA1 (glucocerebrosidase) mutations, and are considered as potential noninvasive biomarkers for predicting those mutations and PD progression. However, their reliability has been questioned, with inadequately investigated genetics, cohorts, and population. In this study, multiple statistical hypothesis tests were employed on urinary BMP levels and sequences of 90 PD-risk single nucleotide polymorphisms (SNPs) from Parkinson's Progression Markers Institution (PPMI) participants. Those SNPs were categorized into four groups based on their impact on BMP levels in various cohorts. Variants rs34637584 G/A and rs34637584 A/A (LRRK2 G2019S) were identified as the most relevant on increasing urinary BMP levels in the PD cohort. Meanwhile, rs76763715 T/T (GBA1) was the primary factor elevating BMP levels in the prodromal cohort compared to its T/C and C/C variants (N370S) and the PD cohort. Proteomics analysis indicated the changed transport pathways may be the reasons for elevated BMP levels in prodromal patients. Our findings demonstrated that higher urinary BMP levels alone were not reliable biomarkers for PD progression or gene mutations but might serve as supplementary indicators for early diagnosis and treatment.

Determinants of tree population temporal stability in a temperate mixed forest over a gradient of nitrogen addition.

Nitrogen (N) deposition is a significant threat to the functioning of forests and negatively impacts the delivery of forest goods and services. Contemporary management approaches seek to adapt forests to such N-deposition stressors, but to date how plant populations in natural forests respond to N deposition and what factors determine the contrasting responses among populations are still unclear. Here, we investigated the impact of N-addition (control: 0 kg ha-1 yr-1; low: 25 kg ha-1 yr-1; medium: 50 kg ha-1 yr-1; high: 75 kg ha-1 ha yr-1) on tree population temporal stability and how initial tree size, mycorrhizal type, and leaf N content (LNC; as a surrogate for functional trait composition) mediate tree population responses to N-addition in a Korean pine and mixed broadleaved dominated temperate forest in northern China. We quantified tree species population temporal stability as the ratio of mean to standard deviation of the year-by-year stem increments recorded in individual trees from 2015 to 2022 experimental period. The results showed different temporal stabilities of tree species among four N-addition levels, with the highest population stability observed within the high N-addition plots. Furthermore, initial tree size had significantly (p < 0.001) positive effects on population temporal stability. The effect of LNC and initial tree size were also contingent on the level of N applied. Specifically, increase in tree population LNC reduced population temporal stability in all plots where N was added. Our results imply that retention of large-sized trees and species with resource-conservative strategies (e.g., low LNC) could enhance forest stability under N deposition.

A tRF-5a fragment that regulates radiation resistance of colorectal cancer cells by targeting MKNK1.

Radiotherapy serves as a crucial strategy in the treatment of colorectal cancer (CRC). However, its efficacy is often hindered by the challenge of radiation resistance. Although the literature suggests that some tRNA-derived small RNAs (tsRNAs) are associated with various cancers, studies reporting the relationship of tsRNAs with cancer cell radiosensitivity have not been published yet. In our study, we utilized tsRNAs sequencing to predict differentially expressed tsRNAs in two CRC cells and their radioresistant cells, and 10 tsRNAs with significant differences in expression were validated by qPCR. The target genes of tRF-16-7X9PN5D were predicted and verified by the bioinformatics, dual-luciferase reporter gene assay and western blotting analyses. Wound healing, colony formation, transwell invasion and CCK-8 assays were performed to detect the effects of tRF-16-7X9PN5D on cell function and radiosensitivity. Western blotting evaluated the relationship between tRF-16-7X9PN5D and the MKNK-eIF4E axis. Our findings demonstrated that tRF-16-7X9PN5D expression was substantially downregulated in radioresistant CRC cells. Furthermore, tRF-16-7X9PN5D could promote CRC cells' ability to proliferate, migrate, invade and obtain radiation resistance by targeting MKNK1. Finally, tRF-16-7X9PN5D could regulate eIF4E phosphorylation via MKNK1. This investigation indicated that tRF-16-7X9PN5D has an essential regulatory role in the radiation resistance of CRC by directly targeting MKNK1, and may be a new pathway for regulating the CRC radiosensitivity.

Diversity and biogeography of plant phyllosphere bacteria are governed by latitude-dependent mechanisms.

Predicting and managing the structure and function of plant microbiomes requires quantitative understanding of community assembly and predictive models of spatial distributions at broad geographic scales. Here, we quantified the relative contribution of abiotic and biotic factors to the assembly of phyllosphere bacterial communities, and developed spatial distribution models for keystone bacterial taxa along a latitudinal gradient, by analyzing 16S rRNA gene sequences from 1453 leaf samples taken from 329 plant species in China. We demonstrated a latitudinal gradient in phyllosphere bacterial diversity and community composition, which was mostly explained by climate and host plant factors. We found that host-related factors were increasingly important in explaining bacterial assembly at higher latitudes while nonhost factors including abiotic environments, spatial proximity and plant neighbors were more important at lower latitudes. We further showed that local plant-bacteria associations were interconnected by hub bacteria taxa to form metacommunity-level networks, and the spatial distribution of these hub taxa was controlled by hosts and spatial factors with varying importance across latitudes. For the first time, we documented a latitude-dependent importance in the driving factors of phyllosphere bacteria assembly and distribution, serving as a baseline for predicting future changes in plant phyllosphere microbiomes under global change and human activities.

High-throughput phenotyping-based quantitative trait loci mapping reveals the genetic architecture of the salt stress tolerance of Brassica napus.

Salt stress is a major limiting factor that severely affects the survival and growth of crops. It is important to understand the salt stress tolerance ability of Brassica napus and explore the underlying related genetic resources. We used a high-throughput phenotyping platform to quantify 2111 image-based traits (i-traits) of a natural population under three different salt stress conditions and an intervarietal substitution line (ISL) population under nine different stress conditions to monitor and evaluate the salt stress tolerance of B. napus over time. We finally identified 928 high-quality i-traits associated with the salt stress tolerance of B. napus. Moreover, we mapped the salt stress-related loci in the natural population via a genome-wide association study and performed a linkage analysis associated with the ISL population, respectively. These results revealed 234 candidate genes associated with salt stress response, and two novel candidate genes, BnCKX5 and BnERF3, were experimentally verified to regulate the salt stress tolerance of B. napus. This study demonstrates the feasibility of using high-throughput phenotyping-based quantitative trait loci mapping to accurately and comprehensively quantify i-traits associated with B. napus. The mapped loci could be used for genomics-assisted breeding to genetically improve the salt stress tolerance of B. napus.

Sarcopenia as a risk factor of progression-free survival in patients with metastases: a systematic review and meta-analysis.

BACKGROUND: Metastasis of cancer causes more than 90% of cancer deaths and is severely damaging to human health. In recent years, several studies have linked sarcopenia to shorter survival in patients with metastatic cancer. Several predictive models exist to predict mortality in patients with metastatic cancer, but have reported limited accuracy. METHODS: We systematically searched Medline, EMBASE, and the Cochrane Library for articles published on or before October 14, 2022. Pooled Hazard Ratio (HR) estimates with 95% confidence intervals (CIs) were calculated using a random effects model. The primary outcome was an increased risk of death or tumor progression in patients with metastatic cancer, which is expressed as progression-free survival (PFS). In addition, we performed subgroup analyses and leave-one-out sensitivity analyses to explore the main sources of heterogeneity and the stability of the results. RESULTS: Sixteen retrospective cohort studies with 1,675 patients were included in the 888 papers screened. The results showed that sarcopenia was associated with lower progression-free survival (HR = 1.56, 95% CI = 1.19-2.03, I2 = 76.3%, P < 0.001). This result was further confirmed by trim-and-fill procedures and leave-one-out sensitivity analysis. CONCLUSIONS: This study suggests that sarcopenia may be a risk factor for reduced progression-free survival in patients with metastatic cancer. Further studies are still needed to explain the reason for this high heterogeneity in outcome. TRIAL REGISTRATION: CRD42022325910.

Biological function and clinical application prospect of tsRNAs in digestive system biology and pathology.

tsRNAs are small non-coding RNAs originating from tRNA that play important roles in a variety of physiological activities such as RNA silencing, ribosome biogenesis, retrotransposition, and epigenetic inheritance, as well as involvement in cellular differentiation, proliferation, and apoptosis. tsRNA-related abnormalities have a significant influence on the onset, development, and progression of numerous human diseases, including malignant tumors through affecting the cell cycle and specific signaling molecules. This review introduced origins together with tsRNAs classification, providing a summary for regulatory mechanism and physiological function while dysfunctional effect of tsRNAs in digestive system diseases, focusing on the clinical prospects of tsRNAs for diagnostic and prognostic biomarkers. Video Abstract.

Ontogeny influences tree growth response to soil fertility and neighbourhood crowding in an old-growth temperate forest.

BACKGROUND AND AIMS: Abiotic and biotic factors simultaneously affect tree growth and thus shape community structure and dynamics. In particular, trees of different size classes show different growth responses to soil nutrients and neighbourhood crowding, but our understanding of how species' joint responses to these factors vary between size classes remains limited in multi-storied temperate forests. Here, we investigated size class differences in tree growth response to soil gradients and neighbourhood crowding in an old-growth temperate forest. METHODS: We combined growth data over 15 years from 38 902 individuals of 42 tree species with trait data in a 25-ha temperate forest plot in northeast China. We built hierarchical Bayesian models of tree growth to examine the effects of soil gradients and neighbourhood crowding between size classes and canopy types. KEY RESULTS: We found that soil and neighbours mainly acted separately in shaping tree growth in small and large trees. Soil total nitrogen and phosphorus increased tree growth in small trees, in particular of understorey species, but not in large trees. Neighbours reduced tree growth in both tree size classes, with stronger effects on large than small trees, and on canopy than understorey species. Furthermore, small trees with higher specific leaf area grew faster in fertile soils, and small trees with less seed mass grew faster in crowded environments. Large trees with higher specific leaf area, specific root length and less seed mass grew faster in crowded environments, while these traits had limited influence on tree growth response to soil gradients. CONCLUSIONS: Our study highlights the importance of size class in modulating the response of tree growth to soil and neighbours, and the differential role of species canopy types and functional traits in capturing these effects in large vs. small trees.

Self-Assembled Cage for In Situ Detecting Silver Cation in Water.

Here, a capsule-shaped cage comprising three monocationic arms was efficiently self-assembled by condensing a triscationic trisaldehyde and a trisamino linkage in water. Multivalence endows the cage with thermodynamic stability in water. Despite its triscationic nature, the cage is able to use its trisimino residue to coordinate a silver cation. As a comparison, other cations lead to cage decomposition or no coordination. The cage and Ag+-coordinated complex were both characterized and confirmed by NMR spectroscopy, mass spectrometry, and theoretical calculations. The metal-ligand complex exhibits a pale-yellow color that can be detectable by the naked eye. The Ag+-coordinated complex undergoes decoordination upon the addition of NaCl, during which the cage containing imine bonds remains intact. Such stability implies that the cage might be potentially employed in silver detection and mining.

Typologies of dependency, household characteristics, and disparity in formal and informal care use: analysis of community-dwelling long-term care insurance claimants in an urban municipality of China.

BACKGROUND: A comprehensive understanding of subgroups of community-dwelling older adults and their long-term care (LTC) utilization can help to promote equality in the long-term services and support system. Dependency and household characteristics were found to affect the LTC utilization of homebound older adults. However, few studies considered the typologies of dependency of older populations according to co-occurring limitations, and little is known about differences in LTC use among elderly of typologies of dependency under distinct household conditions. METHODS: We aimed to identify typologies of dependency of older adults living at home and explore the disparities in formal care and informal care use among typologies of dependency by income and living situation. In this cross-sectional study, we used the public long-term care insurance (LTCI) database of Yiwu, Zhejiang Province, China, and included 1675 individuals aged ≥ 60 years living at home. Cluster analysis was conducted to determine typologies of dependency among older adults. A two-step multilevel analysis was used to examine disparities in formal and informal care use related to household income and living status among typologies of dependency. RESULTS: Seven dependency clusters were identified. Pro-wealthy inequalities in both formal and informal care use were found in the least dependent cluster and the limited-locomotion cluster. Pro-poor inequalities in formal care use were found in the fully dependent cluster without impaired vision and the cluster with intact continence and vision. Living with family members was positively associated with receiving formal care for the fully dependent cluster. Older adults in most clusters were more likely to use informal care when living with family members, except for the least dependent cluster and the limited-locomotion cluster. CONCLUSIONS: Our findings suggest that household inequalities in LTC use varied among typologies of dependency of older adults, which may provide insights for researchers and policymakers to develop tailored LTC and targeted LTCI programs for older adults living at home and their family caregivers, considering both typologies of dependency and household characteristics.

Public participation and outgoing audit of natural resources: Evidence from tripartite evolutionary game in China.

Public participation is essential to the success of ecological civilization. Whether public participation can effectively play a role in the outgoing audit of natural resources (OANR) is an important issue that remains to be explored. This paper uses the tripartite evolutionary game to explore the mechanism of the audit subjects, the leading cadres, and the public in the OANR. The research finds that there is a two-way linkage relationship between the audit subjects and the leading cadres. The audit subjects and the leading cadres affect the behavior strategies of the public in the indirect way and direct way, respectively. However, the public lacks the path to directly affect the other two subjects. The tripartite ideal audit model of "the audit subjects conduct due diligence audits, leading cadres perform duties, the public participate" cannot be realized. The external effect of the public's strategic choice is not enough to make the profit or loss of leading cadres change structurally and then change their behaviors. This paper demonstrates the reasons why the public cannot effectively participate in the OANR at the current stage from three aspects, which are the interpretation of the equations for replication dynamics, the particularity of the audit system, and the effectiveness of public participation. Three suggestions are put forward which are encouraging citizens' indirect participation in the OANR, disclosing information about the OANR, and improving citizens' awareness of the OANR. This paper has important guiding significance for other developing countries to promote public participation in natural resource auditing.

Relationship between person, environmental factors, and activities of daily living performance among physically disabled older adults living at home: a structural equation model.

BACKGROUND: Older adults with physical disability need long-term services and support, which incur enormous costs. However, supportive environments may reduce disability and promote aging in place. It is unclear how the physical and social environment affect different types of functional impairments and influence the performance of activities of daily living (ADL) in physically disabled older adults. OBJECTIVE: The purpose of this study was to examine the relationship between person, environmental factors, and ADL performance among physically disabled older adults living at home. METHODS: This was a cross-sectional study. Using long-term care insurance claims data from a pilot city in China, we used a structural equation model to assess the potential paths among person, environmental factors, and ADL performance. RESULTS: Education and income had different influences on the social environment and physical environment. The functional impairments had significant effects on ADL performance, either directly or through physical environment (with handrails) and social environment (family support). CONCLUSIONS: The present findings offer crucial evidence for understanding the interactions between a person and the environment, as well as their influence on physical ADLs, suggesting the importance of a supportive environment and a subpopulation-targeting strategy for disabled older adults.

Prostate cancer-associated SPOP mutations lead to genomic instability through disruption of the SPOP-HIPK2 axis.

Speckle-type Poz protein (SPOP), an E3 ubiquitin ligase adaptor, is the most frequently mutated gene in prostate cancer. The SPOP-mutated subtype of prostate cancer shows high genomic instability, but the underlying mechanisms causing this phenotype are still largely unknown. Here, we report that upon DNA damage, SPOP is phosphorylated at Ser119 by the ATM serine/threonine kinase, which potentiates the binding of SPOP to homeodomain-interacting protein kinase 2 (HIPK2), resulting in a nondegradative ubiquitination of HIPK2. This modification subsequently increases the phosphorylation activity of HIPK2 toward HP1γ, and then promotes the dissociation of HP1γ from trimethylated (Lys9) histone H3 (H3K9me3) to initiate DNA damage repair. Moreover, the effect of SPOP on the HIPK2-HP1γ axis is abrogated by prostate cancer-associated SPOP mutations. Our findings provide new insights into the molecular mechanism of SPOP mutations-driven genomic instability in prostate cancer.