Pathway choice in the alternative telomere lengthening in neoplasia is dictated by replication fork processing mediated by EXD2's nuclease activity.

Telomerase-independent cancer proliferation via the alternative lengthening of telomeres (ALT) relies upon two distinct, largely uncharacterized, break-induced-replication (BIR) processes. How cancer cells initiate and regulate these terminal repair mechanisms is unknown. Here, we establish that the EXD2 nuclease is recruited to ALT telomeres to direct their maintenance. We demonstrate that EXD2 loss leads to telomere shortening, elevated telomeric sister chromatid exchanges, C-circle formation as well as BIR-mediated telomeric replication. We discover that EXD2 fork-processing activity triggers a switch between RAD52-dependent and -independent ALT-associated BIR. The latter is suppressed by EXD2 but depends specifically on the fork remodeler SMARCAL1 and the MUS81 nuclease. Thus, our findings suggest that processing of stalled replication forks orchestrates elongation pathway choice at ALT telomeres. Finally, we show that co-depletion of EXD2 with BLM, DNA2 or POLD3 confers synthetic lethality in ALT cells, identifying EXD2 as a potential druggable target for ALT-reliant cancers.

Social-cognitive beliefs, alcohol, and tobacco use: a prospective community study of change following a ban on smoking in public places.

OBJECTIVE: To examine social-cognitive change associated with behavior change after the introduction of a smoke-free public places policy. DESIGN: Adults (N = 583) who use public houses licensed to sell alcohol (pubs) completed questionnaires assessing alcohol and tobacco consumption and social-cognitive beliefs 2 months prior to the introduction of the smoking ban in England on July 1, 2007. Longitudinal follow-up (N = 272) was 3 months after the introduction of the ban. MAIN OUTCOME MEASURES: Social-cognitive beliefs, daily cigarette consumption, and weekly alcohol consumption. RESULTS: Smokers consumed considerably more alcohol than did nonsmokers at both time points. However, a significant interaction of Smoking Status x Time showed that while smokers had consumed fewer units of alcohol after the ban, nonsmokers showed an increase over the same period. There was a significant reduction in number of cigarettes consumed after the ban. Subjective norms concerning not smoking, and perceived severity of smoking-related illness increased across time. Negative outcomes associated with not smoking were reduced among former smokers and increased across time among smokers. Regression analyses showed that changes in subjective norm and negative outcome expectancies accounted for significant variance in change in smoking across time. CONCLUSION: Results suggest that the smoking ban may have positive health benefits that are supported by social-cognitive change.

Temporal framing and persuasion to adopt preventive health behavior: moderating effects of individual differences in consideration of future consequences on sunscreen use.

OBJECTIVE: Previous work on temporal framing of health communications has focused upon detection behaviors that possess an inherent immediate risk of negative consequences. The present studies evaluate the role of temporal frame for a preventive behavior, using sunscreen. DESIGN: Two experimental field studies manipulated the temporal frame in which positive and negative consequences of using sunscreen were presented. MAIN OUTCOME MEASURES: Cognitive responses, intention, and behavior (experiment 2). RESULTS: Consistent with hypotheses, Experiment 1 showed that individual differences in consideration of future consequences (CFC; A. Strathman, F. Gleicher, D. S. Boninger, & C. S. Edwards, 1994) moderated (a) the processing of long- versus short-term consequences and (b) the persuasive impact of the different temporal frames on behavioral intentions. In Experiment 2, the balance of positive versus negative thoughts generated by reading the persuasive communications was shown to mediate the effects of the Temporal Frame x CFC interaction on a behavioral measure. CONCLUSION: Findings extend previous work by demonstrating the importance of individual differences in CFC to the processing of health communication about a preventive health behavior and to a behavioral outcome.