The DNA-dependent protein kinase (DNA-PK) has a vital role in DNA double strand break repair and in mediating V(D) J recombination events. Over the years a body of data has implicated DNA-PK playing a significant role in mediating a p53-dependent apoptotic response under a range of cellular conditions including exposure to ionizing radiation (IR), environmental carcinogens and chemotherapeutic agents or in cells that have critically shortened telomeres. These findings raise the hypothesis that DNA-PK acts as both a sensor and transmitter of DNA damage signals that directly impact cell fate. These many overlapping roles are discussed and considered in this review article.

At each step of its life-cycle, human immunodeficiency virus type 1 (HIV-1) interacts with cellular proteins. In some cases, such as the cellular cytidine deaminase APOBEC3G, cellular proteins repress HIV-1 replication. In other cases, cellular proteins serve as essential co-factors, and inhibition of their function blocks HIV-1 replication. This review explores the opportunities for anti-HIV-1 therapy that stem from the recent discoveries that cellular proteins, which are involved in double-strand break DNA repair, are also required for completion of integration of HIV-1 DNA into host cell DNA.

BACKGROUND: Radiation is the only clear etiologic agent for differentiated thyroid cancer (DTC). Understanding the factors affecting sensitivity to gamma radiation and susceptibility to DTC will be critical to early detection and prevention of DTC.
OBJECTIVE: Germline variants of double-strand break repair genes are markers of DTC risk.
OBJECTIVE: Determine the frequency of common single nucleotide polymorphisms of genes of the double-strand break repair pathway in patients with DTC and cancer-free controls.
METHODS: Case-control study.
METHODS: This study included 134 patients with DTC, 79 patients with benign thyroid lesions, and 166 cancer-free control subjects. To avoid ethnic confounding, all subjects were non-Hispanic whites. Genotype analyses were performed on DNA isolated from peripheral blood lymphocytes. Multivariate logistic regression analyses were performed to estimate the risk of DTC associated with each variant genotype.
RESULTS: The XRCC3 18067T polymorphic allele was found significantly more commonly among the DTC cases than for the control subjects (P=.006). After multivariate adjustment, having the XRCC3 18067T allele was associated with an increased risk of DTC (adjusted odds ratio [OR] = 2.1; 95% confidence interval [CI] = 1.3 to 3.4; P = .004). In addition, there was a suggestion that the XRCC3 18067T polymorphic allele was more common among the patients with benign thyroid disease (P = .054), and the homozygous polymorphic genotype was associated with risk for benign thyroid disease (adjusted OR = 2.1; 95% CI = 0.9-4.9; P = .078).
CONCLUSIONS: In this case-control analysis, the XRCC3 18067T polymorphism is associated with DTC risk. However, such work needs confirmation in larger studies.