Dataset Information

The tail that wags the dog: p12, the smallest subunit of DNA polymerase ?, is degraded by ubiquitin ligases in response to DNA damage and during cell cycle progression.

ABSTRACT: DNA polymerase ? (Pol ?) is a key enzyme in eukaryotic DNA replication. Human Pol ? is a heterotetramer whose p12 subunit is degraded in response to DNA damage, leading to the in vivo conversion of Pol ?4 to Pol ?3. Two E3 ubiquitin ligases, RNF8 and CRL4(Cdt2), participate in the DNA damage-induced degradation of p12. We discuss how these E3 ligases integrate the formation of Pol ?3 and ubiquitinated PCNA for DNA repair processes. CRL4(Cdt2) partially degrades p12 during normal cell cycle progression, thereby generating Pol ?3 during S phase. This novel finding extends the current view of the role of Pol ?3 in DNA repair and leads to the hypothesis that it participates in DNA replication. The coordinated regulation of licensing factors and Pol ?3 by CRL4(Cdt2) now opens new avenues for control of DNA replication. A parallel study of Pol ?4 and Pol ?3 in Okazaki fragment processing provides evidence for a role of Pol ?3 in DNA replication. We discuss several new perspectives of the role of the 2 forms of Pol ? in DNA replication and repair, as well the significance of the integration of p12 regulation in DNA repair and cell cycle progression.

SUBMITTER: Lee MY

PROVIDER: S-EPMC3925730 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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The tail that wags the dog: p12, the smallest subunit of DNA polymerase δ, is degraded by ubiquitin ligases in response to DNA damage and during cell cycle progression.

Lee Marietta Y W T MY Zhang Sufang S Lin Szu Hua Sharon SH Wang Xiaoxiao X Darzynkiewicz Zbigniew Z Zhang Zhongtao Z Lee Ernest Y C EY

Cell cycle (Georgetown, Tex.) 20131203 1

DNA polymerase δ (Pol δ) is a key enzyme in eukaryotic DNA replication. Human Pol δ is a heterotetramer whose p12 subunit is degraded in response to DNA damage, leading to the in vivo conversion of Pol δ4 to Pol δ3. Two E3 ubiquitin ligases, RNF8 and CRL4(Cdt2), participate in the DNA damage-induced degradation of p12. We discuss how these E3 ligases integrate the formation of Pol δ3 and ubiquitinated PCNA for DNA repair processes. CRL4(Cdt2) partially degrades p12 during normal cell cycle progr ...[more]

PMID: 24300032

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Project description:ObjectiveTo describe the characteristics of high-frequency hospital users (four or more hospitalizations in a year) and the consequences of including or excluding their data from a readmission-based measure.Data sources2015 and 2016 Massachusetts Medicaid data.Study designWe compare demographics, morbidity burden, and social risk factors for high- and low-frequency hospital users, and membership in 17 accountable care organizations. We evaluate how excluding hospitalizations of high-frequency users from a 30-day readmission measure (with or without risk adjustment) changes its rate and variability and affects performance rankings of accountable care organizations. The outcome is readmission within 30 days; each live discharge from a hospital contributes one observation.Data collection/extraction methodsWe studied 74 706 hospitalizations of 42 794 MassHealth members, 18-64 years old, managed-care-eligible, and ever hospitalized in 2016.Principal findingsAmong adult managed-care-eligible MassHealth members with at least one acute hospitalization, 8.7% were high-frequency hospital users; they contributed 30.2% of hospitalizations and 69.4% of readmissions. High-frequency users were more often male (77.1% vs. 50.0%; P < 0.001) and sicker (mean medical morbidity score was 3.3 vs. 1.9; P < 0.001) than others. They also had significant social risks: 33.1% with housing problems, 44.1% disabled, 83.2% with serious mental illness, and 77.1% with substance abuse disorder (vs. 22.0%, 27.3%, 60.2%, and 50.0%, respectively, for other hospital users [all P values <0.001]). Fully 50.7% of hospitalizations for high-frequency users led to 30-day readmissions (vs. 9.7%), contributing 72.0% of the variance in 30-day readmission, and substantially affecting judgments about the relative performance of accountable care organizations.ConclusionsA small group of high-frequency hospital users have a disproportionate effect on 30-day readmission rates. This negatively affects some Medicaid ACOs, and more broadly is likely to adversely affect safety net hospitals. How these metrics are used should be reconsidered in this context.

Dataset Information

The tail that wags the dog: p12, the smallest subunit of DNA polymerase ?, is degraded by ubiquitin ligases in response to DNA damage and during cell cycle progression.

Publications

The tail that wags the dog: p12, the smallest subunit of DNA polymerase δ, is degraded by ubiquitin ligases in response to DNA damage and during cell cycle progression.

Similar Datasets

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