A CURE Lab in Introductory Biology at a Regional Comprehensive University Negatively Impacts Student Success in the Associated Lecture Course Among Students from Groups Underrepresented in Science.

Course-based undergraduate research experiences (CUREs) have been proposed as a mechanism to democratize access to the benefits of apprentice-style scientific research to a broader diversity of students, promoting inclusivity and increasing student success and retention. As we evaluate CUREs, it is essential to explore their effectiveness within the environments of regional comprehensive universities and community colleges, because they are important access points for a wide variety of students. It is also important to address the potential influence of volunteer bias, where students can opt to enroll in either the CURE or a traditional lab, on the outcomes of CUREs.

Noncanonical outcomes of break-induced replication produce complex, extremely long-tract gene conversion events in yeast.

Long-tract gene conversions (LTGC) can result from the repair of collapsed replication forks, and several mechanisms have been proposed to explain how the repair process produces this outcome. We studied LTGC events produced from repair collapsed forks at yeast fragile site FS2. Our analysis included chromosome sizing by contour-clamped homogeneous electric field electrophoresis, next-generation whole-genome sequencing, and Sanger sequencing across repair event junctions.

Identification of a New Antimicrobial, Desertomycin H, Utilizing a Modified Crowded Plate Technique.

The antibiotic-resistant bacteria-associated infections are a major global healthcare threat. New classes of antimicrobial compounds are urgently needed as the frequency of infections caused by multidrug-resistant microbes continues to rise. Recent metagenomic data have demonstrated that there is still biosynthetic potential encoded in but transcriptionally silent in cultivatable bacterial genomes.

True Grit: Passion and persistence make an innovative course design work.

Our first two experiments on adapting a high-structure course model to an essentially open-enrollment university produced negative or null results. Our third experiment, however, proved more successful: performance improved for all students, and a large achievement gap that impacted underrepresented minority students under traditional lecturing closed. Although the successful design included preclass preparation videos, intensive active learning in class, and weekly practice exams, student self-report data indicated that total study time decreased.

Remarkably Long-Tract Gene Conversion Induced by Fragile Site Instability in Saccharomyces cerevisiae.

Replication stress causes breaks at chromosomal locations called common fragile sites. Deletions causing loss of heterozygosity (LOH) in human tumors are strongly correlated with common fragile sites, but the role of gene conversion in LOH at fragile sites in tumors is less well studied. Here, we investigated gene conversion stimulated by instability at fragile site FS2 in the yeast Saccharomyces cerevisiae In our screening system, mitotic LOH events near FS2 are identified by production of red/white sectored colonies.

Fragile site instability in Saccharomyces cerevisiae causes loss of heterozygosity by mitotic crossovers and break-induced replication.

Loss of heterozygosity (LOH) at tumor suppressor loci is a major contributor to cancer initiation and progression. Both deletions and mitotic recombination can lead to LOH. Certain chromosomal loci known as common fragile sites are susceptible to DNA lesions under replication stress, and replication stress is prevalent in early stage tumor cells.

Sites of genetic instability in mitosis and cancer.

Certain chromosomal regions called common fragile sites are prone to difficulty during replication. Many tumors have been shown to contain alterations at fragile sites. Several models have been proposed to explain why these sites are unstable.

Chromosome aberrations resulting from double-strand DNA breaks at a naturally occurring yeast fragile site composed of inverted ty elements are independent of Mre11p and Sae2p.

Genetic instability at palindromes and spaced inverted repeats (IRs) leads to chromosome rearrangements. Perfect palindromes and IRs with short spacers can extrude as cruciforms or fold into hairpins on the lagging strand during replication. Cruciform resolution produces double-strand breaks (DSBs) with hairpin-capped ends, and Mre11p and Sae2p are required to cleave the hairpin tips to facilitate homologous recombination.

Low levels of DNA polymerase alpha induce mitotic and meiotic instability in the ribosomal DNA gene cluster of Saccharomyces cerevisiae.

The ribosomal DNA (rDNA) genes of Saccharomyces cerevisiae are located in a tandem array of about 150 repeats. Using a diploid with markers flanking and within the rDNA array, we showed that low levels of DNA polymerase alpha elevate recombination between both homologues and sister chromatids, about five-fold in mitotic cells and 30-fold in meiotic cells. This stimulation is independent of Fob1p, a protein required for the programmed replication fork block (RFB) in the rDNA.

Mechanisms of common fragile site instability.

The study of common fragile sites has its roots in the early cytogenetic investigations of the fragile X syndrome. Long considered an interesting component of chromosome structure, common fragile sites have taken on novel significance as regions of the genome that are particularly sensitive to certain forms of replication stress, which are frequently rearranged in cancer cells. In recent years, much has been learned about the genomic structure at fragile sites and the cellular checkpoint functions that monitor their stability.

Chromosomal instability at common fragile sites in Seckel syndrome.

Seckel syndrome (SCKL) is a rare, genetically heterogeneous disorder, with dysmorphic facial appearance, growth retardation, microcephaly, mental retardation, variable chromosomal instability, and hematological disorders. To date, three loci have been linked to this syndrome, and recently, the gene encoding ataxia-telangiectasia and Rad3-related protein (ATR) was identified as the gene mutated at the SCKL1 locus. The ATR mutation affects splicing efficiency, resulting in low levels of ATR in affected individuals.

BRCA1 is required for common-fragile-site stability via its G2/M checkpoint function.

Common fragile sites are loci that form chromosome gaps or breaks when DNA synthesis is partially inhibited. Fragile sites are prone to deletions, translocations, and other rearrangements that can cause the inactivation of associated tumor suppressor genes in cancer cells. It was previously shown that ATR is critical to fragile-site stability and that ATR-deficient cells have greatly elevated fragile-site expression (A.

ATR regulates fragile site stability.

Conditions that partially inhibit DNA replication induce expression of common fragile sites. These sites form gaps and breaks on metaphase chromosomes and are deleted and rearranged in many tumors. Yet, the mechanism of fragile site expression has been elusive.