Interview, survey, and academic transcript data with a diverse sample of first-generation college (FGC) and continuing generation college (CGC) premedical intended emerging adults are analyzed to study academic outcomes and any differences in the availability and use of social capital the first year of college. CGC students know many people with college degrees including those in careers they aspire to obtain, while FGC students do not. All students identify parents as very important forms of social capital who contribute to their success in college, but the types of support differs by educational background. Students whose parents have at least a bachelor's degree (CGC) are "pulled" through their first year with specific advice from their parents about how to succeed in college, while FGC students are "pushed" by their parents with support. In addition, CGC students display evidence of enacting Lareau's concept of concerted cultivation, being much more likely than FGC students to approach and gain assistance from professors, openly critiquing those professors and classes in which they

We have examined the rate and extent of removal of 4'-(hydroxymethyl)-4,5',8-trimethylpsoralen (HMT) cross-linkable monoadducts and interstrand cross-links from restriction fragments within the amplicon containing the dihydrofolate reductase (DHFR) gene in the Chinese hamster ovary (CHO) cell line B11. The rate and extent of removal of HMT cross-links was significantly greater in an actively transcribed fragment than in a nontranscribed extragenic fragment of similar size. For the 5' half of the DHFR gene, approximately 80% of the HMT cross-links were removed in 8 h, in agreement with results reported by Vos and Wauthier [Vos, J. M., & Wauthier, E. L. (1991) Mol. Cell Biol. 11, 2245-2252, 1991]. However, few cross-links were removed in that period from the nontranscribed fragments, whose 5' end is approximately 7 kb downstream from the DHFR transcription unit and which includes a putative replication initiation site. Even after 24 h, only about 50% of the cross-links had been removed from this fragment. In contrast, both the rate and the extent of removal of cross-linkable HMT monoadducts were similar in the two fragments with 50% of the cross-linkable monoadducts removed in 24 h. Moreover, monoadducts formed in the bulk of the genome were removed in 24 h. Moreover, monoadducts formed in the bulk of the genome were removed at a slightly slower rate and to a lesser extent (30% in 24 hours) than those from either of these specific sequences.(ABSTRACT TRUNCATED AT 250 WORDS)

DNA polymerases use an uninterrupted template strand to direct synthesis of DNA. However, some DNA polymerases can synthesize DNA across two discontinuous templates by binding and juxtaposing them, resulting in synthesis across the junction. Primer/template duplexes with 3' overhangs are especially efficient substrates, suggesting that DNA polymerases use the overhangs as regions of microhomology for template synapsis. The formation of these overhangs may be the result of non-template-directed nucleotide addition by DNA polymerases. To examine the relative magnitude and mechanism of template switching, we studied the in vitro enzyme kinetics of template switching and non-template-directed nucleotide addition by the 3'-5' exonuclease-deficient large fragment of Escherichia coli DNA polymerase I. Non-template-directed nucleotide addition and template switching were compared to that of standard primer extension. We found that non-template-directed nucleotide addition and template switching showed similar rates and were approximately 100-fold slower than normal template-directed DNA synthesis. Furthermore, non-template-directed nucleotide addition showed a 10-fold preference for adding dAMP to the ends of DNA over that of the other three nucleotides. For template switching, kinetic analysis revealed that the two template substrates acted as a random bireactant system with mixed-type inhibition of substrate binding by one substrate over the other. These data are the first to establish the binding kinetics of two discontinuous DNA substrates to a single DNA polymerase. Our results suggest that although the activities are relatively weak, non-template-directed nucleotide addition and template switching allow DNA polymerases to overcome breaks in the template strand in an error-prone manner.

DNA polymerases catalyze the synthesis of DNA using a continuous uninterrupted template strand. However, it has been shown that a 3'-->5' exonuclease-deficient form of the Klenow fragment of Escherichia coli DNA polymerase I as well as DNA polymerase of Thermus aquaticus can synthesize DNA across two unlinked DNA templates. In this study, we used an oligonucleotide-based assay to show that discontinuous DNA synthesis was present in HeLa cell extracts. DNA synthesis inhibitor studies as well as fractionation of the extracts revealed that most of the discontinuous DNA synthesis was attributable to DNA polymerase alpha. Additionally, discontinuous DNA synthesis could be eliminated by incubation with an antibody that specifically neutralized DNA polymerase alpha activity. To test the relative efficiency of each nuclear DNA polymerase for discontinuous synthesis, equal amounts (as measured by DNA polymerase activity) of DNA polymerases alpha, beta, delta (+/- PCNA) and straightepsilon (+/- PCNA) were used in the discontinuous DNA synthesis assay. DNA polymerase alpha showed the most discontinuous DNA synthesis activity, although small but detectable levels were seen for DNA polymerases delta (+PCNA) and straightepsilon (- PCNA). Klenow fragment and DNA polymerase beta showed no discontinuous DNA synthesis, although at much higher amounts of each enzyme, discontinuous synthesis was seen for both. Discontinuous DNA synthesis by DNA polymerase alpha was seen with substrates containing 3 and 4 bp single-strand stretches of complementarity; however, little synthesis was seen with blunt substrates or with 1 bp stretches. The products formed from these experiments are structurally similar to that seen in vivo for non-homologous end joining in eukaryotic cells. These data suggest that DNA polymerase alpha may be able to rejoin double-strand breaks in vivo during replication.

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