STK39-mediated amplification of γ-H2A.X promotes homologous recombination and contributes to PARP inhibitor resistance.

The phosphorylation of histone H2A.X into γH2A.X is a crucial early event in the DNA damage response, marking DNA damage sites and initiating repair processes.

Regulation of AMPK activation by extracellular matrix stiffness in pancreatic cancer.

The adenosine monophosphate (AMP)-activated protein kinase (AMPK) sits at a central node in the regulation of energy metabolism and tumor progression. AMPK is best known to sense high cellular ADP or AMP levels, which indicate the depletion of energy stores. Previous studies have shown that the low expression of phosphorylated AMPK is associated with a poor prognosis of pancreatic cancer.

DNA Repair Deficiency Regulates Immunity Response in Cancers: Molecular Mechanism and Approaches for Combining Immunotherapy.

Defects in DNA repair pathways can lead to genomic instability in multiple tumor types, which contributes to tumor immunogenicity. Inhibition of DNA damage response (DDR) has been reported to increase tumor susceptibility to anticancer immunotherapy. However, the interplay between DDR and the immune signaling pathways remains unclear.

Disseminated intravascular coagulopathy: a complication of Stevens-Johnson syndrome/toxic epidermal necrolysis.

Background: The purpose of this study was to retrospectively assess clinical characteristics and mortality rate of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) in patients who developed disseminated intravascular coagulation (DIC).

Methods: A systematic retrospective chart review of all patients with concurrent clinical diagnosis of DIC and SJS/TEN between July 1, 2012, and January 1, 2020, at the Mayo Clinic was performed.

Results: The incidence of DIC in patients with SJS/TEN was 1.

Differences between Stevens-Johnson syndrome versus toxic epidermal necrolysis.

Background: To retrospectively review the outcomes of two rare cutaneous diseases, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN), and to question the practice of averaging the mortality rate on the assumption that they are one disease.

Methods: A retrospective chart review of all patients diagnosed with SJS and TEN by a dermatologist between January 1, 2000, and January 1, 2020, at our institution was performed. Seventy-one patients were identified (21 pediatric and 50 adults).

Use of spironolactone to treat acne in adolescent females.

Background/objectives: Studies assessing the utility of spironolactone for treating acne in adolescent females are lacking. Thus, we sought to examine spironolactone's role in treating this patient population.

Methods: A retrospective review was performed to determine the efficacy of spironolactone treatment in adolescent females seen at Mayo Clinic in Rochester, Minnesota, from 2007 to 2017.

Extracellular matrix stiffness determines DNA repair efficiency and cellular sensitivity to genotoxic agents.

DNA double-strand breaks (DSBs) are highly toxic lesions that can drive genetic instability. These lesions also contribute to the efficacy of radiotherapy and many cancer chemotherapeutics. DNA repair efficiency is regulated by both intracellular and extracellular chemical signals.

Tandem Deubiquitination and Acetylation of SPRTN Promotes DNA-Protein Crosslink Repair and Protects against Aging.

DNA-protein crosslinks (DPCs) are highly toxic DNA lesions that threaten genomic integrity. Recent findings highlight that SPRTN, a specialized DNA-dependent metalloprotease, is a central player in proteolytic cleavage of DPCs. Previous studies suggest that SPRTN deubiquitination is important for its chromatin association and activation.

Author Correction: Regulation of sister chromatid cohesion by nuclear PD-L1.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

STK38 promotes ATM activation by acting as a reader of histone H4 ufmylation.

The ATM (ataxia-telangiectasia mutated) kinase is rapidly activated following DNA damage and phosphorylates its downstream targets to launch DDR signaling. Recently, we and others showed that UFM1 signaling promotes ATM activation. We further discovered that monoufmylation of histone H4 at Lys by UFM1-specific ligase 1 (UFL1) is an important step in the amplification of ATM activation.

The bromodomain containing protein BRD-9 orchestrates RAD51-RAD54 complex formation and regulates homologous recombination-mediated repair.

Homologous recombination (HR) is important for error-free DNA double strand break repair and maintenance of genomic stability. However, upregulated HR is also used by cancer cells to promote therapeutic resistance. Therefore, inducing HR deficiency (HRD) is a viable strategy to sensitize HR proficient cancers to DNA targeted therapies in order to overcome therapeutic resistance.

Regulation of sister chromatid cohesion by nuclear PD-L1.

Programmed death ligand-1 (PD-L1 or B7-H1) is well known for its role in immune checkpoint regulation, but its function inside the tumor cells has rarely been explored. Here we report that nuclear PD-L1 is important for cancer cell sister chromatid cohesion. We found that depletion of PD-L1 suppresses cancer cell proliferation, colony formation in vitro, and tumor growth in vivo in immune-deficient NSG mice independent of its role in immune checkpoint.

The role of poly(ADP-ribose) polymerase inhibitors in the treatment of cancer and methods to overcome resistance: a review.

Poly(ADP-ribose) polymerase (PARP) inhibitors represent one of the successful novel approaches to targeted cancer treatment. Indeed, the US Food and Drug Administration (FDA) has recently approved PARP inhibitors for the treatment of breast and ovarian cancers. Despite the proven efficacy of these agents, certain challenges remain with their use.

Utilization of Cardiac Surveillance Tests in Survivors of Breast Cancer and Lymphoma After Anthracycline-Based Chemotherapy.

Background: The National Comprehensive Cancer Network and American Society of Clinical Oncology recommend consideration of the use of echocardiography 6 to 12 months after completion of anthracycline-based chemotherapy in at-risk populations. Assessment of BNP (B-type natriuretic peptide) has also been suggested by the American College of Cardiology/American Heart Association/Heart Failure Society of America for the identification of Stage A (at risk) heart failure patients. The real-world frequency of the use of these tests in patients after receipt of anthracycline therapy, however, has not been studied previously.

CHK2-FOXK axis promotes transcriptional control of autophagy programs.

Autophagy is an evolutionarily conserved catabolic process, which plays a vital role in removing misfolded proteins and clearing damaged organelles to maintain internal environment homeostasis. Here, we uncovered the checkpoint kinase 2 (CHK2)-FOXK (FOXK1 and FOXK2) axis playing an important role in DNA damage-mediated autophagy at the transcriptional regulation layer. Mechanistically, following DNA damage, CHK2 phosphorylates FOXK and creates a 14-3-3γ binding site, which, in turn, traps FOXK proteins in the cytoplasm.

ZFP161 regulates replication fork stability and maintenance of genomic stability by recruiting the ATR/ATRIP complex.

DNA replication stress-mediated activation of the ATR kinase pathway is important for maintaining genomic stability. In this study, we identified a zinc finger protein, ZFP161 that functions as a replication stress response factor in ATR activation. Mechanistically, ZFP161 acts as a scaffolding protein to facilitate the interaction between RPA and ATR/ATRIP.