Search Results (12)

Grapevine (Vitis vinifera L.) is a key fruit crop affected by abiotic stresses such as salinity, drought, and temperature extremes. The Regulator of Chromosome Condensation 1 (RCC1) family, involved in regulating Ran GTPase activation, nucleocytoplasmic transport, and chromatin organization, has not been comprehensively characterized in grapevine. In this study, we identified 26 VvRCC1 genes, which were classified into five phylogenetic groups, and analyzed their distribution across the grapevine genome. These genes exhibited significant diversity in physicochemical properties, suggesting functional divergence. Expression profiling revealed distinct spatiotemporal patterns, indicating roles in both vegetative growth and reproductive development. Notably, several VvRCC1 genes showed differential responses to salinity, drought, and heat stress. Importantly, VvRCC1-17, identified as UVR8, was shown to regulate anthocyanin biosynthesis under UV-B exposure. OE-VvUVR8 transgenic grape calli exhibited increased anthocyanin accumulation, reflected in a distinct red coloration compared to wild-type calli. This finding links UVR8 to light signaling and pigmentation pathways in grapevine, providing the first comprehensive analysis of the RCC1 gene family in grapevine and highlighting VvRCC1-17 (UVR8) as a key regulator of UV-induced anthocyanin biosynthesis, offering insights into the molecular mechanisms of stress adaptation and pigment regulation. Full article

Quinoa (Chenopodium quinoa Willd.), an Andean crop with exceptional nutritional value, thrives in ecosystems exposed to intense ultraviolet-B (UV-B) radiation; yet the molecular mechanisms underlying its photoreception remain largely unknown. The UV Resistance locus 8 (UVR8) protein, a member of the Regulator of Chromosome Condensation 1 (RCC1) family, is the primary UV-B photoreceptor in plants. Here, we report the first in silico characterization of the RCC1 gene family in C. quinoa, aimed at identifying and structurally analyzing UVR8 homologs. Genomic analysis uncovered 40 CqRCC1 genes, exhibiting extensive structural diversity. Phylogenetic reconstruction identified two proteins, CqRCC1_20 and CqRCC1_23, as the closest homologs of AtUVR8 from Arabidopsis thaliana. Homology modeling revealed that CqRCC1_20 maintains the canonical seven-bladed β-propeller architecture of UVR8, whereas CqRCC1_23 carries a deletion leading to a six-bladed structure. Both isoforms retain the critical tryptophan residues (W233, W285, W337) and the C-terminal Valine-Proline (VP) motif required for photoperception and Constitutive Photomorphogenic 1 (COP1) interaction. Notably, the CqRCC1_23 model predicts fewer hydrogen bonds at the dimer interface and structural alterations at key regulatory interaction sites. Collectively, these results indicate that quinoa harbors functionally conserved UVR8 isoforms with structural divergence, such as CqRCC1_23, which may influence photoreceptor stability and enable a sustained UV-B response, potentially conferring an adaptive advantage in high-radiation environments. Full article

The RCC1 gene is active in ensuring many cellular functions related to cell division in Drosophila melanogaster and Homo sapiens. A detailed comparison of the structure and functions of the RCC1 gene in Drosophila melanogaster and Homo sapiens was carried out using different analytical techniques (bioinformatics, immunofluorescence and confocal microscopy, FISH, and molecular genetic methods). The Drosophila RCC1 gene belongs to the family of housekeeping genes, since it resides in the interbands and gray bands of polytene chromosomes within aquamarine/lazurite chromatin in D. melanogaster. Furthermore, the databases demonstrate that RCC1 in D. melanogaster is expressed in all the tissues at all the developmental stages. According to The Human Protein Atlas, RCC1 in humans also exhibits low tissue specificity for 29 tissues. Immunostaining of polytene chromosomes with RCC1 antibodies revealed approximately 260 sites of RCC1 protein localization exclusively in black bands (sites of developmental genes) and in heterochromatin. The size of the coding gene portions is almost identical for D. melanogaster and H. sapiens, being ~2 kb. The group of Drosophila proteins related to condensed chromatin, RCC1 being a member of this group, has homologs forming similar interaction networks in humans. The conserved nature of the RCC1 gene has been confirmed by cell cycle studies in both species. It was found that expression of the RCC1 gene is upregulated in glioblastoma; the RCC1 protein predominantly resides on centrioles during metaphase. Full article

Abiotic stress affects the growth and development of maize (Zea mays). The regulator of chromosome condensation 1 (RCC1)-containing proteins (RCPs) plays crucial roles in plant growth and development and response to abiotic stresses. However, a comprehensive analysis of the maize RCP family has not been reported in detail. This study presents a systematic bioinformatics analysis of the ZmRCP family, identifying a total of 30 members distributed across nine chromosomes. The physicochemical properties and cis-acting elements in the promoters of ZmRCP members are predicted. The results of subcellular localization showed that ZmRCP3 and ZmRCP10 are targeted to mitochondria and ZmRCP2 is localized in the nucleus. A heatmap of expression levels among family members under abiotic stress conditions revealed varying degrees of induced expression, and the expression levels of 10 ZmRCP members were quantified using RT-qPCR under abiotic stress and plant hormone treatments. The results showed that ZmRCP members exhibit induced or inhibited responses to these abiotic stresses and plant hormones. These results contribute to a better understanding of the evolutionary history and potential role of the ZmRCP family in mediating responses to abiotic stress in maize. Full article

In plants, the essential roles played by the regulator of chromosome condensation 1 (RCC1) in diverse biological processes, including UV-B (ultraviolet-B radiation) response, hormonal signal transduction, cold tolerance and phenotypic plasticity, have been identified. No comprehensive study on the evolution and function of RCC1 gene family in rice has been carried out. A genome-wide analysis of this gene family is thus required. In this study, a total of 26 OsRCC1s unevenly distributed across 10 chromosomes were identified in rice. Based on their phylogenetic relationship and sequence composition, the OsRCC1 family could be classified into six groups. Members within the same group share a similar gene structure and protein motif/domain composition. Gene duplication analysis revealed that segmental duplication might be the main contributor to the expansion of the RCC1 gene family in rice. Several cis-regulatory elements (CREs) relevant to light, abscisic acid (ABA) and methyl jasmonate (MeJA) are abundant in the promoters of OsRCC1s. A large number of microRNA (miRNA) target sites were present in OsRCC1 mRNAs. Additionally, we used data from gene microarray and qRT-PCR to analyze the expression of OsRCC1 genes during various developmental stages and under abiotic stress conditions. OsRCC1s were found to be highly expressed in panicles and seeds, and most OsRCC1s were differentially expressed under abiotic stresses. Taken together, our study provides a systematic characterization of OsRCC1s and preliminarily explores their diversity as well as their biological functions. Evidence demonstrates that OsRCC1s may play vital roles in both development and abiotic stress response. The results presented here lay a foundation for further investigating the functions of OsRCC1s. Full article

A regulator of chromosome condensation 1 (RCC1) family protein has been functionally characterized to be involved in various cellular processes. In this study, one RCC1 gene named SaRCC1 was cloned from the full-length cDNA library of Spartinaalterniflora. The open reading frame (ORF) of SaRCC1 was 1440 bp, and it encoded 479 amino acids with a calculated molecular mass of 51.65 kDa. Multiple amino acid sequence alignments showed that SaRCC1 had high identity with other plant RCC1s, and the phylogenetic analysis indicated that SaRCC1 had a closer affinity to Zea mays RCC1 family protein (ZmRCC1). SaRCC1 gene was induced under salt stress conditions, and its encoded protein was located in peroxisome. In order to further investigate the function of SaRCC1, transgenic Arabidopsis plants ectopically both sense-overexpressing and antisense-overexpressing SaRCC1 were generated. SaRCC1-overexpressing lines exhibited an increased salt and ABA hypersensitivity and reduced resistance to salinity stress. On the other hand, the transcripts of some stress-responsive genes in the SaRCC1 transgenic plants were affected in response to salinity stress. Our results provide evidence for the involvement of SaRCC1, negatively regulating salt stress responses by affecting stress-related gene expression in Arabidopsis. Full article

Protein N-terminal methyltransferase 1 (NTMT1) recognizes a unique N-terminal X-P-K/R motif (X represents any amino acid other than D/E) and transfers 1–3 methyl groups to the N-terminal region of its substrates. Guided by the co-crystal structures of NTMT1 in complex with the previously reported peptidomimetic inhibitor DC113, we designed and synthesized a series of new peptidomimetic inhibitors. Through a focused optimization of DC113, we discovered a new cell-potent peptidomimetic inhibitor GD562 (IC₅₀ = 0.93 ± 0.04 µM). GD562 exhibited improved inhibition of the cellular N-terminal methylation levels of both the regulator of chromosome condensation 1 and the oncoprotein SET with an IC₅₀ value of ~50 µM in human colorectal cancer HCT116 cells. Notably, the inhibitory activity of GD562 for the SET protein increased over 6-fold compared with the previously reported cell-potent inhibitor DC541. Furthermore, GD562 also exhibited over 100-fold selectivity for NTMT1 against several other methyltransferases. Thus, this study provides a valuable probe to investigate the biological functions of NTMT1. Full article

MCPH1, or BRIT1, is often mutated in human primary microcephaly type 1, a neurodevelopmental disorder characterized by a smaller brain size at birth, due to its dysfunction in regulating the proliferation and self-renewal of neuroprogenitor cells. In the last 20 years or so, genetic and cellular studies have identified MCPH1 as a multifaceted protein in various cellular functions, including DNA damage signaling and repair, the regulation of chromosome condensation, cell-cycle progression, centrosome activity and the metabolism. Yet, genetic and animal model studies have revealed an unpredicted essential function of MPCH1 in gonad development and tumorigenesis, although the underlying mechanism remains elusive. These studies have begun to shed light on the role of MPCH1 in controlling various pathobiological processes of the disorder. Here, we summarize the biological functions of MCPH1, and lessons learnt from cellular and mouse models of MCPH1. Full article

Persistent infection of high-risk human papillomavirus (HR-HPV) plays a causal role in cervical cancer. Regulator of chromosome condensation 1 (RCC1) is a critical cell cycle regulator, which undergoes a few post-translational modifications including phosphorylation. Here, we showed that serine 11 (S11) of RCC1 was phosphorylated in HPV E7-expressing cells. However, S11 phosphorylation was not up-regulated by CDK1 in E7-expressing cells; instead, the PI3K/AKT/mTOR pathway promoted S11 phosphorylation. Knockdown of AKT or inhibition of the PI3K/AKT/mTOR pathway down-regulated phosphorylation of RCC1 S11. Furthermore, S11 phosphorylation occurred throughout the cell cycle, and reached its peak during the mitosis phase. Our previous data proved that RCC1 was necessary for the G1/S cell cycle progression, and in the present study we showed that the RCC1 mutant, in which S11 was mutated to alanine (S11A) to mimic non-phosphorylation status, lost the ability to facilitate G1/S transition in E7-expressing cells. Moreover, RCC1 S11 was phosphorylated by the PI3K/AKT/mTOR pathway in HPV-positive cervical cancer SiHa and HeLa cells. We conclude that S11 of RCC1 is phosphorylated by the PI3K/AKT/mTOR pathway and phosphorylation of RCC1 S11 facilitates the abrogation of G1 checkpoint in HPV E7-expressing cells. In short, our study explores a new role of RCC1 S11 phosphorylation in cell cycle regulation. Full article

Meiosis drives reciprocal genetic exchanges and produces gametes with halved chromosome number, which is important for the genetic diversity, plant viability, and ploidy consistency of flowering plants. Alterations in chromosome dynamics and/or cytokinesis during meiosis may lead to meiotic restitution and the formation of unreduced microspores. In this study, we isolated an Arabidopsis mutant male meiotic restitution 1 (mmr1), which produces a small subpopulation of diploid or polyploid pollen grains. Cytological analysis revealed that mmr1 produces dyads, triads, and monads indicative of male meiotic restitution. Both homologous chromosomes and sister chromatids in mmr1 are separated normally, but chromosome condensation at metaphase I is slightly affected. The mmr1 mutant displayed incomplete meiotic cytokinesis. Supportively, immunostaining of the microtubular cytoskeleton showed that the spindle organization at anaphase II and mini-phragmoplast formation at telophase II are aberrant. The causative mutation in mmr1 was mapped to chromosome 1 at the chromatin regulator Male Meiocyte Death 1 (MMD1/DUET) locus. mmr1 contains a C-to-T transition at the third exon of MMD1/DUET at the genomic position 2168 bp from the start codon, which causes an amino acid change G618D that locates in the conserved PHD-finger domain of histone binding proteins. The F1 progenies of mmr1 crossing with knockout mmd1/duet mutant exhibited same meiotic defects and similar meiotic restitution rate as mmr1. Taken together, we here report a hypomorphic mmd1/duet allele that typically shows defects in microtubule organization and cytokinesis. Full article

The regulator of chromosome condensation 1 (RCC1) is the nucleotide exchange factor for a GTPase called the Ras-related nuclear protein, and it is important for nucleo-plasmic transport, mitosis, nuclear membrane assembly, and control of chromatin agglutination during the S phase of mitosis in animals. In plants, RCC1 molecules act mainly as regulating factors for a series of downstream genes during biological processes such as the ultraviolet-B radiation (UV-B) response and cold tolerance. In this study, 56 genes were identified in upland cotton by searching the associated reference genomes. The genes were found to be unevenly distributed on 26 chromosomes, except A06, A12, D03, and D12. Phylogenetic analysis by maximum-likelihood revealed that the genes were divided into five subgroups. The RCC1 genes within the same group shared similar exon/intron patterns and conserved motifs in their encoded proteins. Most genes of the RCC1 family are expressed differently under various hormone treatments and are negatively controlled by salt stress. Gh_A05G3028 and Gh_D10G2310, which encode two proteins located in the nucleus, were strongly induced under salt treatment, while mutants of their homoeologous gene (UVR8) in Arabidopsis and VIGS (virus induced gene silencing) lines of the two genes above in G. hirsutum exhibited a salt-sensitive phenotype indicating their potential role in salt resistance in cotton. These results provide valuable reference data for further study of RCC1 genes in cotton. Full article

The delivery of anticancer agents to their subcellular sites of action is a significant challenge for effective cancer therapy. Peptides, which are integral to several oncogenic pathways, have significant potential to be utilised as cancer therapeutics due to their selectivity, high potency and lack of normal cell toxicity. Novel Ras protein-Regulator of chromosome condensation 1 (Ran-RCC1) inhibitory peptides designed to interact with Ran, a novel therapeutic target in breast cancer, were delivered by entrapment into polyethylene glycol-poly (lactic-co-glycolic acid) PEG-PLGA polymeric nanoparticles (NPs). A modified double emulsion solvent evaporation technique was used to optimise the physicochemical properties of these peptide-loaded biodegradable NPs. The anti-cancer activity of peptide-loaded NPs was studied in vitro using Ran-expressing metastatic breast (MDA-MB-231) and lung cancer (A549) cell lines, and in vivo using Solid Ehrlich Carcinoma-bearing mice. The anti-metastatic activity of peptide-loaded NPs was investigated using migration, invasion and colony formation assays in vitro. A PEG-PLGA-nanoparticle encapsulating N-terminal peptide showed a pronounced antitumor and anti-metastatic action in lung and breast cancer cells in vitro and caused a significant reduction of tumor volume and associated tumor growth inhibition of breast cancer model in vivo. These findings suggest that the novel inhibitory peptides encapsulated into PEGylated PLGA NPs are delivered effectively to interact and deactivate Ran. This novel Ran-targeting peptide construct shows significant potential for therapy of breast cancer and other cancers mediated by Ran overexpression. Full article