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Biomedical subjects

S E Plon

Publications and source records attributed to S E Plon.

26 records · Page 2Linked to original sources
PubMed1993

Cloning of the human homolog of the CDC34 cell cycle gene by complementation in yeast.

In a screen designed to isolate human cDNAs that complement a yeast G2 phase checkpoint mutation (mec1), we isolated a cDNA homologous to the Saccharomyces cerevisiae CDC34 gene. The human CDC34 cDNA can functionally substitute for the yeast CDC34 gene and represents a mammalian homolog of the group of yeast genes required for the late G1-->S phase transition. The human CDC34 gene is expressed in multiple cell lines as a unique species and Southern blot analysis reveals evidence for a single gene that is highly conserved in higher eukaryotes. The human gene is located on the far telomeric region of 19p13.3 in a location that defines a region of homology between human chromosome 19p and mouse chromosome 11.

Anaphase-Promoting Complex-Cyclosome↗
PubMed1986

The use of psoralen-modified DNA to probe the mechanism of enhancer action.

Psoralen-modified DNA was used to study the SV40 enhancer-dependent transcription of the human beta-globin gene. When the enhancer is separated from the beta-globin gene by psoralen adducts on one side and plasmid vector sequences on the other, expression of the gene is strongly inhibited. When placed on the same side of the enhancer as the vector sequences, psoralen adducts have little effect on transcription unless they are located near the transcriptional start site. These results suggest that the inhibition of the transcription of a gene linked to an enhancer in a circular DNA requires the presence of blocking agents on both sides of the gene and that the vector sequences are already blocking enhancer action on one side. Psoralen monoadducts are sufficient to inhibit transcription; the formation of interstrand psoralen cross-links is unnecessary. We assess models for the enhancer mechanism in light of these results.

Base Sequence↗
PubMed1986

Transcription of the human beta-globin gene is stimulated by an SV40 enhancer to which it is physically linked but topologically uncoupled.

One postulated mechanism for how the SV40 enhancer stimulates transcription of linked genes involves the enhancer as a binding site for a sequence-specific "gyrase" activity. We sought to test this hypothesis directly by constructing a novel heteroduplex circle, termed a tailed-circle, in which one of the strands contains an extra palindromic sequence base-paired into a hairpin structure. The human beta-globin gene is placed in the circle and the SV40 enhancer on the hairpin tail, where a bound topoisomerase cannot supercoil the circle. Upon transfection of this DNA into HeLa cells the SV40 enhancer on the hairpin arm is still able to stimulate transcription of the beta-globin gene. Southern blot analysis of the DNA after transfection does not demonstrate any repair or replication of the tailed-circle in vivo. These results argue against the sequence-specific gyrase model for SV40 enhancer action.

DNA Topoisomerases, Type II↗
PubMedDate not supplied

Psychological impact of receiving negative BRCA1 mutation test results in Ashkenazim.

PURPOSE: Most DNA test results for breast/ovarian cancer susceptibility are negative. Because negative test results might be interpreted incorrectly and may have serious psychological and behavioral implications, determining the psychological impact of such results is important. METHODS: A community-based sample of 289 Ashkenazim was tested for 185delAG. The 199 mutation-negatives provided data at baseline and follow-up. Increased risk participants included those who received negative test results but remained at increased risk because positive family and/or personal histories of breast or ovarian cancer made the results uninformative. Average risk meant those who tested negative and had negative family and personal histories of breast or ovarian cancer. Using a logistic regression analysis, both groups' psychological distress levels were compared at baseline and at 1 and 6 months after notification of DNA test results. RESULTS: A logistic regression analysis showed significant but small differences in cancer-specific distress after 6 months between increased and average risk participants (P < 0.006). Increased risk participants reported more distress than average risk. General distress declined among all participants after 1 month. Although baseline and follow-up differences in cancer-specific distress obtained by the increased and average risk participants were statistically significant, none of the absolute levels observed reflected especially high degrees of stress. CONCLUSIONS: Receipt of negative DNA test results does not have a deleterious psychological impact, whether results are informative or uninformative.

Adult↗
PubMedDate not supplied

Mammography behavior after receiving a negative BRCA1 mutation test result in the Ashkenazim: a community-based study.

PURPOSE: To define the impact of a negative BRCA1 test result on subsequent breast cancer screening behavior in women. METHODS: Longitudinal study of a community-based sample of Ashkenazi Jews offered testing for the 185delAG BRCA1 mutation in 1996. Of 309 participants, 118 women were mutation negative, of average risk (based on family history of cancer), unaffected with breast cancer, and provided complete data at baseline, and Year 1 and Year 2 follow-up questionnaires. RESULTS: Women age 50 and older had 91.7% compliance with mammography for the year prior to entry (baseline), 88.3% during Year 1, 91.7% during Year 2 (no significant change; P = 0.775). Women under age 50 demonstrated an increase in mammography (49.2% at baseline, 62.7% Year 1, and 67.1% Year 2; P = 0.035). Both groups demonstrated significant decreases in breast cancer worry and perceived risk. Logistic regression analysis on having a mammogram at Year 2 showed that age, physician recommendation, worry, and perceived risk were all significant. CONCLUSION: Receipt of negative BRCA1 test results in a cohort of Ashkenazi Jewish women did not have a negative impact on mammography behavior 2 years after genetic testing.

Adult↗