e Histone acetyltransferase binding to ORC-1 (HBO1) is a critically important histone acetyltransferase for forming the prereplicative complex (pre-RC) at the replication origin. Pre-RC formation is completed by loading of the MCM2-7 heterohexameric complex, which functions as a helicase in DNA replication. HBO1 recruited to the replication origin by CDT1 acetylates histone H4 to relax the chromatin conformation and facilitates loading of the MCM complex onto replication origins. However, the acetylation status and mechanism of regulation of histone H3 at replication origins remain elusive. HBO1 positively regulates cell proliferation under normal cell growth conditions. Whether HBO1 regulates proliferation in response to DNA damage is poorly understood. In this study, we demonstrated that HBO1 was degraded after DNA damage to suppress cell proliferation. Ser50 and Ser53 of HBO1 were phosphorylated in an ATM/ATR DNA damage sensor-dependent manner after UV treatment. ATM/ATRdependently phosphorylated HBO1 preferentially interacted with DDB2 and was ubiquitylated by CRL4 DDB2 . Replacement of endogenous HBO1 in Ser50/53Ala mutants maintained acetylation of histone H3K14 and impaired cell cycle regulation in response to UV irradiation. Our findings demonstrate that HBO1 is one of the targets in the DNA damage checkpoint. These results show that ubiquitin-dependent control of the HBO1 protein contributes to cell survival during UV irradiation.T ight regulation of genome maintenance processes, including DNA repair, checkpoints, apoptosis, and cell cycle control, prevents DNA instability after DNA damage. Mammalian cells coordinately operate these systems for organism survival, in part through ataxia telangiectasia mutated (ATM) and ATM-and RAD3-related protein (ATR), two critical kinases that function as regulators of major checkpoint pathways. ATM is primarily activated by DNA double-strand breaks (DSBs) (1), and ATR is activated in response to inhibition of DNA replication (2). Activated ATM and ATR phosphorylate histone H2AX to recruit DNA repair proteins (3) and also checkpoint kinase 1 (Chk1) to suppress cell cycle progression (4, 5). Chk1 indirectly inhibits dephosphorylation of Tyr15 of cyclin-dependent kinase 2 (CDK2) (6) and CDC2 via Cdc25A degradation (7). ATM and ATR also phosphorylate the p53 tumor suppressor to increase its protein stability (8). p53 is a critical cellular factor that induces apoptosis genes (9) and the p21 CDK inhibitor gene (10, 11). Thus, substrates of ATM and ATR are involved in arresting the cell cycle, repairing DNA, and eliminating damaged cells by apoptosis.Histone acetyltransferase binding to ORC-1 (HBO1) was originally identified as an ORC1 binding protein (12) and acts as a cofactor in the prereplicative complex (pre-RC) (13). This histone acetyltransferase (HAT) associates with distinct complexes to acetylate histones H3 and H4 (14, 15). HBO1 is also involved in cell proliferation control through regulating the expression of multiple genes in the p53 pathway (16). A previous ...

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Background: To improve the postoperative prognosis of patients with lung cancer, predicting the recurrence high-risk patients is needed for the efficient application of adjuvant chemotherapy. However, predicting lung cancer recurrence after a radical surgery is difficult even with conventional histopathological prognostic factors, thereby a novel predictor should be identified. As lipid metabolism alterations are known to contribute to cancer progression, we hypothesized that lung adenocarcinomas with high recurrence risk contain candidate lipid predictors. This study aimed to identify candidate lipid predictors for the recurrence of lung adenocarcinoma after a radical surgery.Methods: Frozen tissue samples of primary lung adenocarcinoma obtained from patients who underwent a radical surgery were retrospectively reviewed. Recurrent and non-recurrent cases were assigned to recurrent (n = 10) and non-recurrent (n = 10) groups, respectively. Extracted lipids from frozen tissue samples were subjected to liquid chromatography-tandem mass spectrometry analysis. The average total lipid levels of the non-recurrent and recurrent groups were compared. Candidate predictors were screened by comparing the folding change and P-value of t-test in each lipid species between the recurrent and non-recurrent groups.Results: The average total lipid level of the recurrent group was 1.65 times higher than that of the non-recurrent group (P < 0.05). A total of 203 lipid species were increased (folding change, ≥2; P < 0.05) and 4 lipid species were decreased (folding change, ≤0.5; P < 0.05) in the recurrent group. Among these candidates, increased sphingomyelin (SM)(d35:1) in the recurrent group was the most prominent candidate predictor, showing high performance of recurrence prediction (AUC, 9.1; sensitivity, 1.0; specificity, 0.8; accuracy, 0.9).Conclusion: We propose SM(d35:1) as a novel candidate predictor for lung adenocarcinoma recurrence. Our finding can contribute to precise recurrence prediction and qualified postoperative therapeutic strategy for lung adenocarcinomas.Abbreviations: AUC, area under the ROC curve; ROC, receiver operating characteristic.

Objective 18F-FDG PET/CT has been reported useful for diagnosing aortic graft infection. However, 18F-FDG uptake may depend upon various factors including open vs endovascular repair and time from surgery. We aimed to elucidate the factors influencing its uptake and the diagnostic value of 18F-FDG PET/CT after open and endovascular repair. Methods Hospital database of PET/CT (N = 14490) and our departmental database were cross-checked to identify those who underwent 18F-FDG PET/CT after aortic repair. Patient’s data were retrieved from the chart. Images were reviewed by two nuclear medicine specialists in consensus, and the presence of increased 18F-FDG uptake was recorded. The maximum standardized uptake value (SUV max) was measured. Results Among the 1112 patients who underwent aortic repair between 2011 and 2022, 71 patients were identified. Eighteen patients underwent 18F-FDG PET/CT for suspected graft infection and the remaining 53 patients for other purposes (malignancy etc.). Fourteen patients were treated as aortic graft infection. They had significantly higher SUV max than those without graft infection (mean 8.64 (SD2.78) vs 3.40 (SD0.84); p &lt; 0.01). In the non-infected grafts, SUV max was higher early after open surgical repair, while it remained low after endovascular repair. Conclusion After endovascular aortic repair, a constant cut-off value of “SUV max = 4.5” seems appropriate for diagnosing graft infection, since it remains low and stable from the early postoperative period. After open surgical repair, it seems acceptable to have “stepwise cut-off value” depending on the time from surgery.