Recognition of BACH1 quaternary structure degrons by two F-box proteins under oxidative stress.

Ubiquitin-dependent proteolysis regulates diverse cellular functions with high substrate specificity, which hinges on the ability of ubiquitin E3 ligases to decode the targets' degradation signals, i.e., degrons.

Relationship of post-treatment radiological findings with relapses in idiopathic granulomatous mastitis patients.

Objective: The aim of this study is to investigate the relationship between post-treatment radiological findings and recurrences in idiopathic granulomatous mastitis (IGM).

Methods: Clinical data, ultrasound (US) and magnetic resonance imaging (MRI) examinations of 160 patients with IGM (mean age 34.6±7 years; range 20-56 years) who received only steroid or steroid+surgical treatment were evaluated retrospectively.

Nucleoporins cooperate with Polycomb silencers to promote transcriptional repression and repair at DNA double strand breaks.

DNA Double-strand breaks (DSBs) are harmful lesions and major sources of genomic instability. Studies have suggested that DSBs induce local transcriptional silencing that consequently promotes genomic stability. Several factors have been proposed to actively participate in this process, including ATM and Polycomb repressive complex 1 (PRC1).

Stabilization of GTSE1 by cyclin D1-CDK4/6-mediated phosphorylation promotes cell proliferation: relevance in cancer prognosis.

In healthy cells, cyclin D1 is expressed during the G1 phase of the cell cycle, where it activates CDK4 and CDK6. Its dysregulation is a well-established oncogenic driver in numerous human cancers. The cancer-related function of cyclin D1 has been primarily studied by focusing on the phosphorylation of the retinoblastoma (RB) gene product.

CDK-independent role of D-type cyclins in regulating DNA mismatch repair.

Although mismatch repair (MMR) is essential for correcting DNA replication errors, it can also recognize other lesions, such as oxidized bases. In G0 and G1, MMR is kept in check through unknown mechanisms as it is error-prone during these cell cycle phases. We show that in mammalian cells, D-type cyclins are recruited to sites of oxidative DNA damage in a PCNA- and p21-dependent manner.

Visualizing Single-Stranded DNA Foci in the G1 Phase of the Cell Cycle.

DNA has dedicated cellular repair pathways capable of coping with lesions that could arise from both endogenous and/or exogenous sources. DNA repair necessitates collaboration between numerous proteins, responsible for covering a broad range of tasks from recognizing and signaling the presence of a DNA lesion to physically repairing it. During this process, tracks of single-stranded DNA (ssDNA) are often created, which are eventually filled by DNA polymerases.

A noncanonical function of SKP1 regulates the switch between autophagy and unconventional secretion.

Intracellular degradation of proteins and organelles by the autophagy-lysosome system is essential for cellular quality control and energy homeostasis. Besides degradation, endolysosomal organelles can fuse with the plasma membrane and contribute to unconventional secretion. Here, we identify a function for mammalian SKP1 in endolysosomes that is independent of its established role as an essential component of the family of SCF/CRL1 ubiquitin ligases.

A membrane-associated MHC-I inhibitory axis for cancer immune evasion.

Immune-checkpoint blockade has revolutionized cancer treatment, but some cancers, such as acute myeloid leukemia (AML), do not respond or develop resistance. A potential mode of resistance is immune evasion of T cell immunity involving aberrant major histocompatibility complex class I (MHC-I) antigen presentation (AP). To map such mechanisms of resistance, we identified key MHC-I regulators using specific peptide-MHC-I-guided CRISPR-Cas9 screens in AML.

Outcomes of high-risk breast lesions diagnosed using image-guided core needle biopsy: results from a multicenter retrospective study.

Purpose: The clinical management of high-risk lesions using image-guided biopsy is challenging. This study aimed to evaluate the rates at which such lesions were upgraded to malignancy and identify possible predictive factors for upgrading high-risk lesions.

Methods: This retrospective multicenter analysis included 1.

CDT1, a licensing factor that limits rereplication.

Cells must avoid licensing of neosynthesized DNA to prevent rereplication. In this issue of Molecular Cell, Ratnayeke et al. (2022) reveal how the licensing factor CDT1, prior to its degradation, inhibits DNA elongation by suppressing CMG helicase progression at replication forks.

Relationship of chest computed tomography score with disease severity and laboratory values in children with COVID-19.

Aim: Although chest computed tomography (CT) score has been well evaluated in adult coronavirus disease (COVID-19), its use in paediatric cases is insufficiently studied. Our aim is to evaluate the relationship of chest CT score with disease severity and laboratory parameters.

Methods: Seventy-six paediatric patients with confirmed COVID-19 and chest CT evaluation on admission have been included in this study.

The NSP14/NSP10 RNA repair complex as a Pan-coronavirus therapeutic target.

The risk of zoonotic coronavirus spillover into the human population, as highlighted by the SARS-CoV-2 pandemic, demands the development of pan-coronavirus antivirals. The efficacy of existing antiviral ribonucleoside/ribonucleotide analogs, such as remdesivir, is decreased by the viral proofreading exonuclease NSP14-NSP10 complex. Here, using a novel assay and in silico modeling and screening, we identified NSP14-NSP10 inhibitors that increase remdesivir's potency.

Correlation of neuroimaging and thorax CT findings in patients with COVID-19: A large single-center experience.

Background/aim: The aim of this current study was to describe the neuroimaging findings among patients with COVID-19 and to compare them with thorax CT imaging findings and clinicobiological profiles.

Materials And Methods: Between the period March 11 and December 31, 2020, we evaluated brain computed tomography (CT) and magnetic resonance (MR) images of patients with COVID-19. A total of 354 patients (mean age 65.

Laser Micro-Irradiation to Study DNA Recruitment During S Phase.

DNA damage repair maintains the genetic integrity of cells in a highly reactive environment. Cells may accumulate various types of DNA damage due to both endogenous and exogenous sources such as metabolic activities or UV radiation. Without DNA repair, the cell's genetic code becomes compromised, undermining the structures and functions of proteins and potentially causing disease.

Influenza A (H1N1)-Associated Acute Necrotizing Encephalopathy with Unusual Posterior Reversible Encephalopathy Syndrome in a Child.

Other than respiratory symptoms, influenza A (H1N1) can rarely cause neurological complications in children and adults. In this article, we aimed to present H1N1-associated acute necrotizing encephalopathy (ANE) and asymmetrical involvement of posterior reversible encephalopathy syndrome (PRES) in a 30-month-old male patient with clinical and radiological imaging findings. The patient who presented to the hospital with febrile convulsion and lethargy had elevated liver enzymes and coagulopathy.

CRL4 is a master regulator of D-type cyclins.

D-type cyclins are central regulators of the cell division cycle and are among the most frequently deregulated therapeutic targets in human cancer, but the mechanisms that regulate their turnover are still being debated. Here, by combining biochemical and genetics studies in somatic cells, we identify CRL4 (also known as CRL4) as the ubiquitin ligase that targets all three D-type cyclins for degradation. During development, loss of Ambra1 induces the accumulation of D-type cyclins and retinoblastoma (RB) hyperphosphorylation and hyperproliferation, and results in defects of the nervous system that are reduced by treating pregnant mice with the FDA-approved CDK4 and CDK6 (CDK4/6) inhibitor abemaciclib.

AMBRA1 regulates cyclin D to guard S-phase entry and genomic integrity.

Mammalian development, adult tissue homeostasis and the avoidance of severe diseases including cancer require a properly orchestrated cell cycle, as well as error-free genome maintenance. The key cell-fate decision to replicate the genome is controlled by two major signalling pathways that act in parallel-the MYC pathway and the cyclin D-cyclin-dependent kinase (CDK)-retinoblastoma protein (RB) pathway. Both MYC and the cyclin D-CDK-RB axis are commonly deregulated in cancer, and this is associated with increased genomic instability.

Diagnostic value of MDCT in determining the perinephric fat tissue and renal sinus invasion in patients with clear cell renal cell carcinoma.

Aims: To investigate the accuracy of multidetector computed tomography (MDCT) findings, and the effect of tumor volume in determining the perinephric and renal sinus invasion in clear cell renal cell carcinomas (ccRCCs).

Method: Fifty patients with ccRCCs underwent non-contrast and nephrographic-phase contrast-enhanced MDCT examination before total nephrectomy. The following MDCT features were used to diagnose perinephric fat tissue invasion: perinephric stranding, perinephric vascularity, and irregular contour.

ORF10-Cullin-2-ZYG11B complex is not required for SARS-CoV-2 infection.

In order to understand the transmission and virulence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), it is necessary to understand the functions of each of the gene products encoded in the viral genome. One feature of the SARS-CoV-2 genome that is not present in related, common coronaviruses is ORF10, a putative 38-amino acid protein-coding gene. Proteomic studies found that ORF10 binds to an E3 ubiquitin ligase containing Cullin-2, Rbx1, Elongin B, Elongin C, and ZYG11B (CRL2).

Should CT be used for the diagnosis of RT-PCR-negative suspected COVID-19 patients?

Introduction: The diagnosis of patients with Coronavirus disease 2019 (COVID-19) suspicion but negative reverse transcriptase-polymerase chain reaction (RT-PCR) test is challenging.

Objective: We aimed to investigate the diagnostic value of chest computed tomography (CT) in RT-PCR-negative patients with suspected COVID-19.

Materials And Methods: The study included patients who were admitted to our hospital with the suspicion of COVID-19 between 1 April 2020 and 30 April 2020 and tested negative after RT-PCR test, and underwent CT for further diagnosis.

The Efficacy of Chest Computed Tomography in Pediatric Patients With Suspected COVID-19.

Objective: The aim of the study was to investigate chest computed tomography (CT) findings and the value of CT in the diagnosis in children with suspected coronavirus disease 2019 (COVID-19).

Materials And Methods: Chest CT images of pediatric patients with suspected COVID-19 were retrospectively evaluated. Computed tomography findings were divided into 3 groups: normal, consistent, and inconsistent with COVID-19.

Genome-wide alterations of uracil distribution patterns in human DNA upon chemotherapeutic treatments.

Numerous anti-cancer drugs perturb thymidylate biosynthesis and lead to genomic uracil incorporation contributing to their antiproliferative effect. Still, it is not yet characterized if uracil incorporations have any positional preference. Here, we aimed to uncover genome-wide alterations in uracil pattern upon drug treatments in human cancer cell line models derived from HCT116.

Interaction between NSMCE4A and GPS1 links the SMC5/6 complex to the COP9 signalosome.

Background: The SMC5/6 complex, cohesin and condensin are the three mammalian members of the structural maintenance of chromosomes (SMC) family, large ring-like protein complexes that are essential for genome maintenance. The SMC5/6 complex is the least characterized complex in mammals; however, it is known to be involved in homologous recombination repair (HRR) and chromosome segregation.

Results: In this study, a yeast two-hybrid screen was used to help elucidate novel interactions of the kleisin subunit of the SMC5/6 complex, NSMCE4A.