The homologous recombination (HR) repair pathway maintains genetic integrity after DNA double-strand break (DSB) damage and is particularly crucial for maintaining fidelity of expressed genes. Histone H4 acetylation on lysine 16 (H4K16ac) is associated with transcription, but how pre-existing H4K16ac directly affects DSB repair is not known. To answer this question, we used CRISPR/Cas9 technology to introduce I-SceI sites, or repair pathway reporter cassettes, at defined locations within gene-rich (high H4K16ac/euchromatin) and gene-poor (low H4K16ac/heterochromatin) regions. The frequency of DSB repair by HR is higher in gene-rich regions. Interestingly, artificially targeting H4K16ac at specific locations using gRNA/dCas9-MOF increases HR frequency in euchromatin. Finally, inhibition/depletion of RNA polymerase II or Cockayne syndrome B protein leads to decreased recruitment of HR factors at DSBs. These results indicate that the pre-existing H4K16ac status at specific locations directly influences the repair of local DNA breaks, favoring HR in part through the transcription machinery.
Background: Sleeve resection allows for preservation of lung parenchyma and improved long-term outcomes when compared with pneumonectomy. Little is known about minimally invasive sleeve resection, especially indications, feasibility, technical aspects, complications, and outcomes. We reviewed our institutional experience with sleeve resections via a minimally invasive approach. Methods: We performed a retrospective review of a prospectively maintained database from 01/01/2010 to 11/01/2017. Indications, operative details, pathology, postoperative complications were reviewed and longerterm follow-up was reviewed. Results: Fifteen patients were identified (5 males, 10 females). Details are presented in Table 1. Patients ranged in age from 7 to 82 years (median, 57 years). Approaches included video-assisted thoracoscopic surgery (VATS) and robotic. Airway sleeve resection was performed in all patients with an additional arterioplasty in 4, one patient having a double sleeve. Length of stay ranged from 3 to 10 days (median, 5 days). Indication for surgery included carcinoid in 5 (1 atypical), NSCLC in 6, and 4 additional pathologies. Complications occurred in 6 patients: air leak [2], pericardial effusion [1], transient brachial plexopathy [1], and atrial fibrillation [2]. There were no anastomotic complications. Median follow-up was 4.2 years. There were no anastomotic strictures. Conclusions: In experienced centers, sleeve resection via a minimally invasive approach is feasible with acceptable morbidity and mortality. Results in this small series appear comparable with the open approach.
We hope that our article can inspire the young minds to further grow the field and take it to higher levels.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.