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M Banerjee

Publications and source records attributed to M Banerjee.

At least 55 records · Page 3Linked to original sources
PubMed1999

Lymph node size does not correlate with the presence of prostate cancer metastasis.

OBJECTIVES: To determine whether lymph node size is a surrogate marker for lymph node metastasis. METHODS: We reviewed 980 patients who underwent radical retropubic prostatectomy with bilateral pelvic lymph node dissection for clinically localized prostate cancer, of whom 63 had lymph node metastases. A comparable group of patients with prostate cancer undergoing radical prostatectomy who did not have lymph node involvement was identified using the following parameters: serum prostate-specific antigen level, clinical and pathologic stage, and pre- and postoperative Gleason score. The axial and longitudinal dimensions of the nodes from patients with and without metastases were analyzed to assess the significance of lymph node size in predicting the presence of metastases. All patients had negative preoperative computed tomography (CT) and bone scans. Of the 63 patients with lymph node metastases, 48 had tissue available for measuring the dimensions of the lymph nodes. RESULTS: A total of 76 metastatic and 92 negative lymph nodes were identified from the patients with and without metastatic nodes, respectively. The mean nodal longitudinal size was 1.65 cm (range 0.2 to 6.5) and 3.50 cm (range 0.5 to 9) for positive and negative nodes, respectively (P = 0.0001). The mean axial nodal size was 0.8 cm (range 0.2 to 3.2) and 1.0 cm (range 0.2 to 2.2) for positive and negative lymph nodes, respectively. In 56 metastatic nodes (74%), the axial size was less than 1 cm and in 20 (26%) less than 5 mm. CONCLUSIONS: Lymph node size should not be used as a surrogate for the presence of lymph node metastases. Although no patient had enlarged lymph nodes by CT scan criteria (greater than 1.5 cm), 6 (8%) of 48 and 19 (12%) of 48 patients with and without lymph node metastases, respectively, had nodes with an axial dimension greater than 1.5 cm.

Aged↗
PubMed1999

Correlation of bcl-2 oncoprotein immunohistochemical expression with proliferation index and histopathologic parameters in colorectal neoplasia.

Thebcl-2oncogene plays an important role in carcinogenesis by inhibiting cell death (apoptosis). It was initially discovered in follicular B cell lymphoma with t(14,18), and subsequently found in other malignant and premalignant lesions. Alteration of the normal controls of cell proliferation is also a significant factor in the multistep process of tumorigenesis. The proliferative activity of a given lesion is commonly valuated by MIB1, a monoclonal antibody to Ki67 proliferation antigen. Immuno-histochemical (IHC) staining expression of bcl-2 and Ki67 was retrospectively investigated in a series of 52 colorectal carcinomas and 56 adenomas according to the avidin-biotin-complex method. The aim of the study was twofold: 1) to investigate any correlation between MIB1 and bcl-2 immunostaining expression in colonic adenomas and carcinomas, 2) to identify any relationship between either marker and several histopathologic parameters including tumor size, pathologic stage, lymph node metastasis, angio-lymphatic invasion, tumor grade and differentiation in colon carcinomas. Bcl-2 was consistently higher in adenomas than in carcinomas. There were 44/56 (78.6%) adenomas, and 27/52 (51.9%) carcinomas positive for bcl-2 (p=0.004). The mean Ki67 labeling index (LI) was 30.05+/-7.6 and 38.12+/-11.01 in adenomas and carcinomas, respectively (p=0.0001). Expression of bcl-2 in carcinoma was significantly associated with a lower mean Ki67 LI and with favorable histopathologic parameters. We conclude that bcl-2 oncoprotein expression is probably an early step in the process of colon carcinogenesis, and its expression may be associated with a favorable clinical course. Furthermore, an inverse relationship exists between bcl-2 and Ki67 in colonic neoplasia. Evaluation of bcl-2 and Ki67 IHC expression in colonic carcinoma should be performed prospectively to determine if their expression is of value in predicting the clinical course in these patients.

Adenocarcinoma↗
PubMed1999

Replacement of the bacteriophage Mu strong gyrase site and effect on Mu DNA replication.

The bacteriophage Mu strong gyrase site (SGS) is required for efficient replicative transposition and functions by promoting the synapsis of prophage termini. To look for other sites which could substitute for the SGS in promoting Mu replication, we have replaced the SGS in the middle of the Mu genome with fragments of DNA from various sources. A central fragment from the transposing virus D108 allowed efficient Mu replication and was shown to contain a strong gyrase site. However, neither the strong gyrase site from the plasmid pSC101 nor the major gyrase site from pBR322 could promote efficient Mu replication, even though the pSC101 site is a stronger gyrase site than the Mu SGS as assayed by cleavage in the presence of gyrase and the quinolone enoxacin. To look for SGS-like sites in the Escherichia coli chromosome which might be involved in organizing nucleoid structure, fragments of E. coli chromosomal DNA were substituted for the SGS: first, repeat sequences associated with gyrase binding (bacterial interspersed mosaic elements), and, second, random fragments of the entire chromosome. No fragments were found that could replace the SGS in promoting efficient Mu replication. These results demonstrate that the gyrase sites from the transposing phages possess unusual properties and emphasize the need to determine the basis of these properties.

Bacteriophage mu↗
PubMed1999

Results of a clinical care pathway for radical prostatectomy patients in an open hospital - multiphysician system.

OBJECTIVES: The object of this study was to evaluate the results of a comprehensive clinical care pathway (CCP) aimed at reducing the length of hospitalization and overall cost for patients undergoing radical prostatectomy in a setting including both academic and private physicians. METHODS: The clinical records of 1,129 consecutive patients who underwent radical prostatectomy by 24 urologists between July 1, 1990, and December 31, 1996, were reviewed. The factors considered were length of stay, morbidity and mortality, readmission rates, and average cost. The CCP was implemented on January 1, 1994. Its scope was to minimize preoperative evaluation, eliminate the preoperative hospital stay, standardize postoperative care and provide intensive patient education. RESULTS: The average length of stay decreased significantly after implementation of the CCP (8.1 vs. 4.9 days, p = 0.0001). In 1990, there was a large difference in length of stay between academic and private physicians (8.3 vs. 12.6 days) (p = 0. 02) but by 1 year after implementation of the CCP there was virtually no difference (4.69 vs. 4.71 days) (p > 0.05). Complication rates were similar before and after implementation of the CCP. Using the average 1993 cost/case as the baseline preCCP figure, the average cost of radical prostatectomy decreased by 16% in 1994 and by 22% in 1995. CONCLUSIONS: It is possible to successfully implement a CCP in a multi-physician system to reduce length of stay and cost of radical prostatectomy without subjecting the patient to a greater risk of complication.

Costs and Cost Analysis↗
PubMed1999

Evolution of the high molecular weight glutenin loci of the A, B, D, and G genomes of wheat.

We used PCR to obtain phylogenetically informative sequences from the high molecular weight glutenin genes of wheat. The validity of partial sequence comparisons as a means of studying glutenin phylogenetics was established by constructing neighbour-joining trees from partial alignments of 12 published glutenin allele sequences. PCR was then used to obtain 20 novel glutenin allele sequences from various Triticum and Aegilops species, including a 3000 year old preserved wheat. A neighbour-joining tree derived from all known glutenin allele sequences had eight clades, representing the eight loci from which the allele sequences were derived, and was split into two halves, one comprising alleles from the Glu-1-1 loci and the other comprising Glu-1-2 alleles. The topology was compatible with the postulated relationships between the A, B, D, and G genomes. The Glu gene duplication event was tentatively dated at 7.2-10.0 million years ago (MYA), the origin of the four genomes at 5.0-6.9 MYA, and the split between the B and G genomes at 2.5-3.5 MYA. The Glu-B1-1 alleles in cultivated wheats fell into two subgroups that diverged 1.4-2.0 MYA, suggesting that emmer was domesticated twice. The D allele sequences were relatively diverse, indicating that the hybridization event that resulted in the hexaploid bread wheats might have occurred more than once.

Base Sequence↗
PubMed1998

Racial differences and prognostic significance of tumor location in radical prostatectomy specimens.

BACKGROUND: Our objective was to evaluate radical prostatectomy specimens for possible racial differences in tumor location, as well as to correlate tumor location with pathologic stage and disease-free survival. METHODS: Between January 1991-December 1997, 1,245 patients underwent radical prostatectomy with bilateral pelvic lymphadenectomy for clinically localized prostate cancer. Seven hundred and eighty-five patients who were treated with surgery as monotherapy were evaluated. Tumor location, defined as mainly anterior, mainly posterior, or both (anterior and posterior), was obtained from review of tumor maps prepared from pathological evaluation of completely embedded, resected specimens. RESULTS: Overall tumor location was anterior in 107 (14%), posterior in 459 (58%), and both in 219 (28%) cases. The incidence of anterior tumors was higher in African American men compared to Caucasians (16% vs. 11%, P = 0.045). The rate of positive surgical margins in anteriorly and posteriorly located tumors was 60% vs. 38% in African American men (P = 0.001) and 48% vs. 27% in Caucasians (P = 0.001), respectively. African American men were found to have a higher incidence of positive surgical margins (50%; 174/348) compared to Caucasian men (34%; 150/437; P = 0.001). CONCLUSIONS: Anterior tumors were present in 14% of our patients. African American men have a greater percentage of anterior tumors than do Caucasians. In addition, a higher rate of positive surgical margins was encountered in patients with anterior tumors, especially if they were African American men. In patients with an abnormal serum prostate-specific antigen level and negative sextant prostate biopsies, we recommend biopsy of the anterior zone of the prostate.

Adult↗
PubMed1998

Prognostic indicators in patients with seminal vesicle involvement following radical prostatectomy for clinically localized prostate cancer.

PURPOSE: We identify prognostic factors in patients with seminal vesicle involvement and negative lymph nodes following radical prostatectomy for clinically localized prostate cancer. MATERIALS AND METHODS: A total of 93 patients who underwent radical prostatectomy and had seminal vesicle invasion without lymph node metastasis were evaluated. Patients who underwent neoadjuvant/adjuvant hormonal or radiation therapy were excluded from study. Preoperative serum prostate specific antigen (PSA), biopsy and radical prostatectomy specimen Gleason score, surgical margin status, presence of extraprostatic extension and evidence of biochemical disease progression were determined prospectively. Biochemical failure was defined as a single serum PSA elevation greater than 0.4 ng./ml. RESULTS: The presence of positive surgical margins (p = 0.001), and Gleason score 7 or higher from preoperative biopsies (p = 0.03) and from the radical prostatectomy specimen (p = 0.01) were significant predictors of disease progression at a median followup of 43.3 months. Patients with preoperative PSA less than 10 ng./ml. had a better disease-free survival (p = 0.07). On multivariate analysis, after adjusting for biopsy Gleason score, prostatectomy Gleason score and serum PSA, positive surgical margins remained a statistically significant predictor of disease progression (p = 0.002). CONCLUSIONS: Surgical margin status is an independent predictor of disease recurrence in patients with seminal vesicle involvement and negative lymph nodes following radical prostatectomy. Serum PSA 10 ng./ml. or greater and specimen Gleason score 7 or greater also were adverse prognostic factors in these patients. Conversely, patients with negative surgical margins and lymph nodes have a better prognosis than previously expected, despite seminal vesicle invasion.

Aged↗
PubMed1998

Salvage surgery or salvage radiotherapy for locally recurrent prostate cancer.

OBJECTIVES: To evaluate the efficacy and toxicity of salvage radiation or surgery for locally recurrent tumor after initial treatment for clinically localized prostate cancer. METHODS: The treatment records of 70 patients with local treatment failure after definitive therapy for clinically localized prostate cancer were reviewed. Initial treatment consisted of external beam radiation therapy (RT) in 27 patients and radical retropubic prostatectomy (RP) in 43 patients. RESULTS: The mean serum PSA levels were similar in both groups before initial treatment: 8.5 and 10.5 ng/mL for the salvage RP and salvage RT groups, respectively (P = 0.09). However, at the time of salvage treatment, the mean serum PSA levels were 9.1 and 1.1 ng/mL for the salvage RP and salvage RT groups, respectively (P = 0.0001). The mean time from tumor recurrence to salvage treatment was 15.6 months for the salvage RP group and 4.9 months for the salvage RT group (P = 0.0001 ). Although there was no statistical difference in the disease-free survival rate (P = 0.38), a trend for better disease control in the salvage RT group was evident (74.4% versus 44.4%). Patients treated with salvage RP had a higher rate of urinary incontinence than those undergoing salvage RT: 63% and 32.6%, respectively (P = 0.01). CONCLUSIONS: The disease-free survival rate was similar between patients receiving salvage RP or RT, despite the significantly higher serum PSA levels at the time of treatment and the delay in time to treatment for the salvage RP patients. Salvage RP is associated with a high rate of urinary incontinence. Earlier identification of tumor recurrence after RT may improve the efficacy and safety of salvage RP.

Follow-Up Studies↗
PubMed1998

Tick-borne relapsing fever in British Columbia, Canada: first isolation of Borrelia hermsii.

The spirochete that causes tick-borne relapsing fever, Borrelia hermsii, was isolated in pure culture during 1995 and 1996 from three acutely ill human patients infected in southern British Columbia, Canada. The geographic area of exposure is a known focus of this disease dating back to 1930 when the first case was recognized in a human. Analyses of plasmid DNA, protein profiles, and reactivity with a species-specific monoclonal antibody identified the new isolates of spirochetes as B. hermsii, all of which were most similar to an isolate of this spirochete from northern California described previously. These are the first reported isolates of B. hermsii from Canada.

Adult↗
PubMed1998

Posttranslational regulation of Ty1 retrotransposition by mitogen-activated protein kinase Fus3.

Ty1 retrotransposons in Saccharomyces cerevisiae are maintained in a state of transpositional dormancy. We isolated a mutation, rtt100-1, that increases the transposition of genomic Ty1 elements 18- to 56-fold but has little effect on the transposition of related Ty2 elements. rtt100-1 was shown to be a null allele of the FUS3 gene, which encodes a haploid-specific mitogen-activated protein kinase. In fus3 mutants, the levels of Ty1 RNA, protein synthesis, and proteolytic processing were not altered relative to those in FUS3 strains but steady-state levels of TyA, integrase, and reverse transcriptase proteins and Ty1 cDNA were all increased. These findings suggest that Fus3 suppresses Ty1 transposition by destabilizing viruslike particle-associated proteins. The Fus3 kinase is activated through the mating-pheromone response pathway by phosphorylation at basal levels in naive cells and at enhanced levels in pheromone-treated cells. We demonstrate that suppression of Ty1 transposition in naive cells requires basal levels of Fus3 activation. Substitution of conserved amino acids required for activation of Fus3 derepressed Ty1 transposition. Moreover, epistasis analyses revealed that components of the pheromone response pathway that act upstream of Fus3, including Ste4, Ste5, Ste7, and Ste11, are required for the posttranslational suppression of Ty1 transposition by Fus3. The regulation of Ty1 transposition by Fus3 provides a haploid-specific mechanism through which environmental signals can modulate the levels of retrotransposition.

Calcium-Calmodulin-Dependent Protein Kinases↗
PubMed1998

Antibody responses in melanoma patients immunized with an anti-idiotype antibody mimicking disialoganglioside GD2.

We initiated a clinical trial for patients with advanced malignant melanoma treated with an anti-idiotype antibody that mimics the disialoganglioside GD2. We report the clinical and immune responses of the first 12 patients entered into this trial. Patients received 1-, 2-, 4-, or 8-mg doses of the anti-idiotype antibody mixed with 100 microg of QS-21 adjuvant every other week, four times, and then monthly. Twelve patients have been on trial for 2-23 months, and all of them have generated immune responses. Patients were removed from the study if they demonstrated disease progression. Hyperimmune sera from all 12 patients revealed an anti-anti-idiotypic Ab3 response, as demonstrated by the inhibition of Ab2 binding to Ab1 by patients' immune sera. To further test the anti-anti-idiotypic response, patients' Ab3 antibodies were affinity purified on Sepharose 4B columns containing adsorbed immunizing anti-idiotype immunoglobulin. Purified Ab3 of all patients studied inhibited binding of Ab1 to a GD2-positive cell line. Purified Ab3 also inhibited binding of Ab1 to purified GD2, in a manner comparable to equal quantities of purified Ab1. The patient Ab3 was truly an Ab1' because it specifically bound to purified disialoganglioside GD2. The isotypic specificity of the Ab3 antibody was predominantly IgG, with only minimal IgM. The predominant IgG subclass was IgG1, with approximately equal quantities of IgG2, IgG3, and IgG4. These Ab3 antibodies reacted specifically with tumor cells expressing GD2 by immune flow cytometry and immunoperoxidase assays. Five patients' Ab3 antibodies studied for antibody-dependent cellular cytotoxicity were positive. One patient had a complete clinical response, with resolution of soft tissue disease, and six patients had stable disease, ranging from 9 to 23 months, and are being continued on vaccine therapy. Toxicity consisted of local reaction at the site of the injection, including induration and pain that generally resolved within a few days. Mild fever and chills were observed in 75% of the patients but rarely required acetaminophen. There was no additional toxicity, including abdominal pain that was previously seen with infusion of murine monoclonal anti-GD2 antibody. Current trials include patients with stage III melanoma and small cell lung cancer. Future trials will attempt to enhance the antitumor response by the addition of interleukin 2, granulocyte macrophage colony-stimulating factor, and other cytokines, together with the 1A7 vaccine.

Adult↗
PubMed1998

A similar pattern of chromosomal alterations in prostate cancers from African-Americans and Caucasian Americans.

A combination of genetic and epigenetic factors may explain the disproportionate incidence and mortality of prostate cancer among African-American males (AAMs) as compared with Caucasian American males (CAMs). We wished to determine whether primary prostate cancers from AAMs and CAMs harbor different patterns or frequencies of chromosomal alterations. Comparative genomic hybridization (CGH) was performed on clinically localized, untreated primary prostate cancers from 16 AAMs and 16 CAMs. Detailed statistical analysis was used to delineate gains and deletions with high sensitivity and specificity and to compare the frequency and pattern of alterations between the two groups of tumors. The two groups of patients had indistinguishable preoperative serum prostate-specific antigen levels, and the two groups of tumors had similar pathological stages and grades. Chromosomal gains and deletions occurred in regions known to be frequently altered in prostate cancer. Specifically, the most frequent alterations were deletions of regions on chromosomes 13q, 5q, 16q, and 8p and gains of regions on 8q and 5q. When tumors from AAMs and CAMs were compared, the frequencies of alteration (deletion, gain, or no alteration) were similar across 98.9% of the length of the genome. The patterns of alterations of the most frequently altered chromosomes were also similar between tumors from AAMs and CAMs. We concluded that primary prostate cancers from AAMs and CAMs harbor a similar pattern and frequency of chromosomal alterations. These data support the notion that sporadic prostate cancers from AAMs and CAMs develop by similar chromosomal mechanisms. Biological differences, if present, do not occur on the chromosomal level.

Black People↗
PubMed1998

A clinicobacteriological study on leucorrhoea.

The pathogens like Trichomonas vaginalis (4.5%), N gonorrhoeae (2.7%) and C albicans (6.7%) were exclusively present in leucorrhoea. The other potential agents with their respective percentages in normal women and cases of leucorrhoea were U urealyticum (21.2% and 50.2%), actinomyces (29.7% and 41.6%), Chlamydia trachomatis (17% and 48.8%), candida-like organisms (CLO) (1.2% and 9.5%) and non-group B streptococci (4.2% and 16.7%). The percentages of urethral syndrome (65.8%), vaginal irritation (63.4%), sore vulva (17%), cervicitis (13.4%), cervical erosion (11%) of the STD clinic were more than those of gynaecological cases. The latter group more often revealed infertility (15.8%) and pelvic inflammatory disease (13.6%). The exclusive isolation rate of N gonorrhoeae (7.3%) and prevalence of G vaginalis (19.5%) and Trichomonas vaginalis (8.5%) in the STD clinic were notable. The cases of gynaecological clinic more commonly showed C albicans (8%) and CLO (13.6%). Significant differences pertaining to U urealyticum (leucorrhoea and inapparent group p < 0.01; leucorrhoea and normal cases p < 0.01), M hominis (leucorrhoea and inapparent group p < 0.05; leucorrhoea and normal cases p < 0.01), Chlamydia trachomatis (leucorrhoea and normal cases p < 0.01) and also actinomyces (leucorrhoea and normal cases p < 0.01; inapparent and normal cases p < 0.05) were recorded. There was conspicuous association of U urealyticum, M hominis, G vaginalis, Chlamydia trachomatis, CLO and actinomyces with leucorrhoea. An almost exclusive presence of Staph aureus, Esch coli and Klebsiella in cases of leucorrhoea appeared meaningful.

Cervix Uteri↗
PubMed1998

Effect of neoadjuvant androgen deprivation on circulating prostate cells in the bone marrow of men undergoing radical prostatectomy.

Our objective was to determine the effect of neoadjuvant hormonal therapy on the presence of circulating prostate cells in patients undergoing radical prostatectomy for prostate cancer. A total of 60 patients at high risk for extraprostatic disease were analyzed for the presence of circulating prostate cells using reverse transcriptase PCR (RTPCR) amplification of the prostate-specific antigen mRNA. Twenty-nine patients underwent radical prostatectomy for a clinical T2b-c tumor or a stage T1c-T2a tumor and a serum prostate-specific antigen level > or =10ng/ml (radical prostatectomy alone), and 31 similarly staged patients received neoadjuvant hormonal therapy before radical prostatectomy (neoadjuvant). Bone marrow samples were used for RTPCR analysis. Twenty-four percent and 58% of the radical-prostatectomy-alone patients and neoadjuvant patients had organ-confined disease, respectively (P = 0.007). In the radical-prostatectomy-alone group, 77% and 14% of patients with extraprostatic and organ-confined disease were RTPCR positive, respectively (P = 0.03). However, in the neoadjuvant group, 46% and 28% of patients with extraprostatic and organ-confined disease were RTPCR positive, respectively (P = 0.29). For patients that were RTPCR positive, 45 % of the neoadjuvant patients had organ-confined disease compared with 6% in the radical-prostatectomy-alone patients (P = 0.018). These data suggest that a subset of the neoadjuvant patients are converted to organ confined disease without eliminating the prostate cells in the bone marrow. Our data suggest that hormonal therapy before radical prostatectomy decreases the occurrence of extraprostatic disease but, to a lesser degree, the incidence of circulating prostate cells. This may partially explain why hormonal therapy before radical prostatectomy has not improved disease-free survival.

Androgen Antagonists↗
PubMed1998

Limited role of radionuclide bone scintigraphy in patients with prostate specific antigen elevations after radical prostatectomy.

PURPOSE: Bone scintigrams of patients with increasing serum prostate specific antigen (PSA) after radical prostatectomy are only rarely positive. We identify clinical parameters that would improve our ability to select patients for this imaging study. MATERIALS AND METHODS: We reviewed all bone scintigrams done at our institution between 1991 and 1996 in patients with persistently increasing serum PSA after radical prostatectomy. What prompted the clinician to obtain the bone scintigram was trigger PSA (tPSA). The rate of increase in PSA to tPSA was measured by tPSA/time from radical prostatectomy (slope 1) and tPSA/time from last undetectable PSA (slope 2). These parameters were evaluated together with standard clinicopathological data in univariate and multivariate analyses to determine the ability to predict the bone scintigram result. RESULTS: In univariate analysis tPSA (p = 0.003), slope 1 (p = 0.005) and slope 2 (p = 0.004) were useful in predicting the bone scintigram result but pathological stage, Gleason score, preoperative PSA and time to recurrence were not. In multivariate analysis the single most useful parameter in predicting the bone scintigram result was tPSA (p = 0.01). Based on a logistic regression model the probability of a positive bone scintigram was less than 5% until tPSA increased to 40 to 45 ng./ml. CONCLUSIONS: In patients with increasing serum PSA after radical prostatectomy current serum PSA is the best predictor of the bone scintigram result. Furthermore, there is limited usefulness of bone scintigraphy until PSA increases above 30 to 40 ng./ml.

Bone Neoplasms↗
PubMed1997

Are there ethnic differences in deletions in the dystrophin gene?

We studied 160 cases of Duchenne muscular dystrophy (DMD) drawn from all parts of India, using multiplex PCR of 27 exons. Of these, 103 (64.4%) showed intragenic deletions. Most (69.7%) of the deletions involved exons 45-51. The phenotype of cases with deletion of single exons did not differ significantly from those with deletion of multiple exons. The distribution of deletions in studies from different countries was variable, but this was accounted for either by the small number of cases studied, or by fewer exons analyzed. It is concluded that there is likely to be no ethnic difference with respect to deletions in the DMD gene.

Adolescent↗
PubMed1997

Transcriptional silencing of Ty1 elements in the RDN1 locus of yeast.

We demonstrate that in Saccharomyces cerevisiae, the tandem array of ribosomal RNA genes (RDN1) is a target for integration of the Ty1 retrotransposon that results in silencing of Ty1 transcription and transposition. Ty1 elements transpose into random rDNA repeat units and are mitotically stable. In addition, we have found that mutation of several putative modifiers of RDN1 chromatin structure abolishes silencing of Ty1 elements in the rDNA array. Disruption of SIR2, which elevates recombination in RDN1, or TOP1, which increases psoralen accessibility in rDNA, or HTA1-HTB1, which reduces histone H2A-H2B levels and causes localized chromatin perturbations, abolishes transcriptional silencing of Ty1 elements in RDN1. Furthermore, deletion of the gene for the ubiquitin conjugating enzyme Ubc2p, which ubiquitinates histones in vitro, derepresses not only Ty1 transcription but also mitotic recombination in RDN1. On the basis of these results, we propose that a specialized chromatin structure exists in RDN1 that silences transcription of the Ty1 retrotransposon.

Base Sequence↗