Elongation factor ELOF1 drives transcription-coupled repair and prevents genome instability

Correct transcription is crucial for life. However, DNA damage severely impedes elongating RNA polymerase II, causing transcription inhibition and transcription-replication conflicts. Cells are equipped with intricate mechanisms to counteract the severe consequence of these transcription-blocking lesions. However, the exact mechanism and factors involved remain largely unknown. Here, using a genome-wide CRISPR-Cas9 screen, we identified the elongation factor ELOF1 as an important factor in the transcription stress response following DNA damage. We show that ELOF1 has an evolutionarily conserved role in transcription-coupled nucleotide excision repair (TC-NER), where it promotes recruitment of the TC-NER factors UVSSA and TFIIH to efficiently repair transcription-blocking lesions and resume transcription. Additionally, ELOF1 modulates transcription to protect cells against transcription-mediated replication stress, thereby preserving genome stability. Thus, ELOF1 protects the transcription machinery from DNA damage via two distinct mechanisms

The weekend effect in patients hospitalized for upper gastrointestinal bleeding: A single-center 10-year experience

OBJECTIVE: This study was conducted to assess the possible weekend effect in patients with upper gastrointestinal bleeding (UGIB) on the basis of a 10-year single-center experience in Serbia. MATERIALS AND METHODS: A retrospective analysis of hospital records in the University Clinic 'Dr Dragisa Misovic-Dedinje', Belgrade, Serbia, from 2002 to 2012 was conducted. Patients admitted for UGIB were identified, and data on demographic characteristics, symptoms, drug use, alcohol abuse, diagnosis and treatment were collected. Univariate and multivariate logistic regression were used to assess the association between weekend admission and the occurrence of rebleeding and in-hospital mortality. RESULTS: Analyses included 493 patients. Rebleeding occurred significantly more frequently on weekends (45.7 vs. 32.7%, P=0.004). Weekend admission [odds ratio (OR)=1.78; 95% confidence interval (CI): 1.15-2.74], older age (OR=1.02; 95% CI: 1.00-1.03), and the presence of both melaena and hematemesis (OR=2.29; 95% CI: 1.29-4.07) were associated with the occurrence of rebleeding. No difference between weekend and weekday admissions was observed for the in-hospital mortality rate (6.9% vs. 6.0%, P=0.70). Older age (OR=1.14; 95% CI: 1.08-1.20), presentation with melaena and hematemesis (OR=4.12; 95% CI: 1.56-10.90) and need for surgical treatment (OR=5.16; 95% CI: 1.61-16.53) were significant predictors of all-cause mortality. Patients with nonvariceal bleeding had significantly higher rebleeding rates on weekends (44 vs. 32.3%, P=0.013). CONCLUSION: There was no significant weekend effect in the mortality of patients admitted for UGIB, irrespective of the source of bleeding. Increased attention to older patients presenting with a more severe clinical picture is needed to prolong survival and prevent rebleeding. \ua9 2014 Wolters Kluwer Health | Lippincott Williams & Wilkins

The weekend effect in patients hospitalized for upper gastrointestinal bleeding

OBJECTIVE: This study was conducted to assess the possible weekend effect in patients with upper gastrointestinal bleeding (UGIB) on the basis of a 10-year single-center experience in Serbia. MATERIALS AND METHODS: A retrospective analysis of hospital records in the University Clinic 'Dr Dragisa Misovic-Dedinje', Belgrade, Serbia, from 2002 to 2012 was conducted. Patients admitted for UGIB were identified, and data on demographic characteristics, symptoms, drug use, alcohol abuse, diagnosis and treatment were collected. Univariate and multivariate logistic regression were used to assess the association between weekend admission and the occurrence of rebleeding and in-hospital mortality. RESULTS: Analyses included 493 patients. Rebleeding occurred significantly more frequently on weekends (45.7 vs. 32.7%, P=0.004). Weekend admission [odds ratio (OR)=1.78; 95% confidence interval (CI): 1.15-2.74], older age (OR=1.02; 95% CI: 1.00-1.03), and the presence of both melaena and hematemesis (OR=2.29; 95% CI: 1.29-4.07) were associated with the occurrence of rebleeding. No difference between weekend and weekday admissions was observed for the in-hospital mortality rate (6.9% vs. 6.0%, P=0.70). Older age (OR=1.14; 95% CI: 1.08-1.20), presentation with melaena and hematemesis (OR=4.12; 95% CI: 1.56-10.90) and need for surgical treatment (OR=5.16; 95% CI: 1.61-16.53) were significant predictors of all-cause mortality. Patients with nonvariceal bleeding had significantly higher rebleeding rates on weekends (44 vs. 32.3%, P=0.013). CONCLUSION: There was no significant weekend effect in the mortality of patients admitted for UGIB, irrespective of the source of bleeding. Increased attention to older patients presenting with a more severe clinical picture is needed to prolong survival and prevent rebleeding