The translocation activity of Rad54 reduces crossover outcomes during homologous recombination.

Homologous recombination (HR) is a template-based DNA double-strand break repair pathway that requires the selection of an appropriate DNA sequence to facilitate repair. Selection occurs during a homology search that must be executed rapidly and with high fidelity. Failure to efficiently perform the homology search can result in complex intermediates that generate genomic rearrangements, a hallmark of human cancers. Rad54 is an ATP dependent DNA motor protein that functions during the homology search by regulating the recombinase Rad51. How this regulation reduces genomic exchanges is currently unknown. To better understand how Rad54 can reduce these outcomes, we evaluated several amino acid mutations in Rad54 that were identified in the COSMIC database. COSMIC is a collection of amino acid mutations identified in human cancers. These substitutions led to reduced Rad54 function and the discovery of a conserved motif in Rad54. Through genetic, biochemical and single-molecule approaches, we show that disruption of this motif leads to failure in stabilizing early strand invasion intermediates, causing increased crossovers between homologous chromosomes. Our study also suggests that the translocation rate of Rad54 is a determinant in balancing genetic exchange. The latch domain's conservation implies an interaction likely fundamental to eukaryotic biology.

Health plan selection criteria by people with impaired mobility.

BACKGROUND: Many decision-support tools for consumers selecting a health plan include a module measuring peer-group satisfaction with service and quality of care. The most widely used tools are sufficient for most people, but fail to report measures that are important to many individuals with disabilities. OBJECTIVES: To elicit health plan selection and assessment criteria by groups of people with one type of functional impairment arising from different origins. RESEARCH DESIGN: Observational study and qualitative analysis of structured focus groups. Content analysis of CAHPS survey instruments. SUBJECTS: Each participant had a mobility impairment arising from spinal cord injury, cerebral palsy, rheumatoid arthritis, or multiple sclerosis. Each participant had a choice of health plans. Focus groups were conducted in Phoenix, Philadelphia, and Washington DC. RESULTS: People with mobility impairments arising from the studied conditions desire comparative health plan information on the reliability of transportation to medical appointments, the ability to use an experienced and knowledgeable specialist as a primary provider, and accessible buildings and examination equipment. This study population also seeks information about the experience of their peers in each health plan, especially about benefits administration. CONCLUSIONS: People with mobility impairments arising from spinal cord injury, cerebral palsy, multiple sclerosis, or rheumatoid arthritis currently have little information and little bona fide choice of health plans and physicians. This group of people seeks specific information within the areas of benefit coverage, benefits interpretation and administration, provider panels, accessibility to clinics and equipment, and how to navigate the health plan's grievance and appeals process.