Cell Size Checkpoint Control by the Retinoblastoma Tumor Suppressor Pathway

Size control is essential for all proliferating cells, and is thought to be regulated by checkpoints that couple cell size to cell cycle progression. The aberrant cell-size phenotypes caused by mutations in the retinoblastoma (RB) tumor suppressor pathway are consistent with a role in size checkpoint control, but indirect effects on size caused by altered cell cycle kinetics are difficult to rule out. The multiple fission cell cycle of the unicellular alga Chlamydomonas reinhardtii uncouples growth from division, allowing direct assessment of the relationship between size phenotypes and checkpoint function. Mutations in the C. reinhardtii RB homolog encoded by MAT3 cause supernumerous cell divisions and small cells, suggesting a role for MAT3 in size control. We identified suppressors of an mat3 null allele that had recessive mutations in DP1 or dominant mutations in E2F1, loci encoding homologs of a heterodimeric transcription factor that is targeted by RB-related proteins. Significantly, we determined that the dp1 and e2f1 phenotypes were caused by defects in size checkpoint control and were not due to a lengthened cell cycle. Despite their cell division defects, mat3, dp1, and e2f1 mutants showed almost no changes in periodic transcription of genes induced during S phase and mitosis, many of which are conserved targets of the RB pathway. Conversely, we found that regulation of cell size was unaffected when S phase and mitotic transcription were inhibited. Our data provide direct evidence that the RB pathway mediates cell size checkpoint control and suggest that such control is not directly coupled to the magnitude of periodic cell cycle transcription

Factors Affecting Occupational Exposure to Needlestick and Sharps Injuries among Dentists in Taiwan: A Nationwide Survey

BACKGROUND: Although the risks of needlestick and sharps injuries (NSIs) for dentists are well recognized, most papers published only described the frequency of occupational exposure to NSIs. Less has been reported assessing factors contributing to exposure to NSIs. The purpose of this study was to update the epidemiology of NSIs among dentists in Taiwan and identify factors affecting NSIs in order to find preventive strategies. METHODOLOGY/PRINCIPAL FINDINGS: A nationwide survey was conducted in dentists at 60 hospitals and 340 clinics in Taiwan. The survey included questions about factors supposedly affecting exposure to NSIs, such as dentist and facility characteristics, knowledge and attitudes about infectious diseases, and practices related to infection control. Univariate and multivariate logistic regression analyses were conducted to determine the association between risk factors and exposure to NSIs. In total, 434 (74.8%) of 580 dentists returned the survey questionnaires, and 100 (23.0%) reported that they had experienced more than one NSI per week. Our data showed that the risk of occupational NSIs is similarly heightened by an older age (odds ratio [OR], 3.18; 95% confidence interval [CI], 1.62-6.25), more years in practice (OR, 2.57; 95% CI, 1.41-4.69), working in clinics (OR, 1.73; 95% CI, 1.08-2.77), exhibiting less compliance with infection-control procedures (OR, 1.82; 95% CI, 1.04-3.18), having insufficient knowledge of blood-borne pathogens (OR, 1.67; 95% CI, 1.04-2.67), and being more worried about being infected by blood-borne pathogens (OR, 1.82; 95% CI, 1.05-3.13). CONCLUSIONS/SIGNIFICANCE: High rates of NSIs and low compliance with infection-control procedures highly contribute to the chance of acquiring a blood-borne pathogen infection and threaten occupational safety. This study reveals the possible affecting factors and helps in designing prevention strategies for occupational exposure to NSIs

Regulated overexpression of AGL15: effects on abscission and senescence in reproductive tissues

[[sponsorship]]農業生物科技研究中心[[note]]已出版;沒有審查制度;具代表

Candidate retinoblastoma (Rb) pathway target genes identified by extragenic suppressors of a Mat3 null mutation in Chlamydomonas

[[sponsorship]]農業生物科技研究中心[[note]]已出版;沒有審查制度;具代表

SMT15 connects sulfur-related cellular response to cell cycle control in Chlamydomonas

[[sponsorship]]農業生物科技研究中心[[note]]已出版;有審查制度;具代表

A screen for suppressors of an RB mutation in Chlamydomonas identifies conserved and novel cell size checkpoint regulators

[[sponsorship]]農業生物科技研究中心[[note]]已出版;有審查制度;具代表

A Suppressor Screen in Chlamydomonas Identifies Novel Components of the Retinoblastoma Tumor Suppressor Pathway

The retinoblastoma (RB) protein is a eukaryotic tumor suppressor and negative cell-cycle regulator. Chlamydomonas reinhardtii cells that lack the RB homolog MAT3 show loss of size checkpoint control and deregulated cell-cycle progression leading to the production of tiny cells. We carried out an insertional mutagenesis screen to isolate bypass suppressors of mat3 (smt mutants) that reverted the mat3 cell-size defect. Previously we reported that the loci encoding Chlamydomonas homologs of E2F and DP were frequently disrupted in this screen, indicating that the architecture of the canonical RB pathway is conserved in Chlamydomonas with MAT3/RB acting as a negative regulator upstream of E2F/DP. Here, we describe four novel smt mutants that moderately suppressed the cell-size checkpoint and cell-cycle phenotypes of mat3. As single mutants, three of the smt strains displayed no obvious phenotypes, and one had a slightly small phenotype. Strikingly, several smt double-mutant combinations synergized to cause enhanced suppression of mat3 and even to cause a large-cell phenotype that is comparable to that caused by loss of DP1. Molecular characterization of one smt mutant revealed that suppression is due to a defect in a gene encoding a putative small ubiquitin-like modifier (SUMO) peptidase. Our results reveal a complex genetic network that lies downstream of MAT3/RB and implicate protein sumoylation as an important step for cell-cycle progression in cells that are missing MAT3/RB