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1.
J Biol Chem ; 299(4): 104590, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36889585

RESUMEN

Thymine DNA glycosylase (TDG) is a multifaceted enzyme involved in several critical biological pathways, including transcriptional activation, DNA demethylation, and DNA repair. Recent studies have established regulatory relationships between TDG and RNA, but the molecular interactions underlying these relationships are poorly understood. Herein, we now demonstrate that TDG binds directly to RNA with nanomolar affinity. Using synthetic oligonucleotides of defined length and sequence, we show that TDG has a strong preference for binding G-rich sequences in single-stranded RNA but binds weakly to single-stranded DNA and duplex RNA. TDG also binds tightly to endogenous RNA sequences. Studies with truncated proteins indicate that TDG binds RNA primarily through its structured catalytic domain and that its disordered C-terminal domain plays a key role in regulating TDG's affinity and selectivity for RNA. Finally, we show that RNA competes with DNA for binding to TDG, resulting in the inhibition of TDG-mediated excision in the presence of RNA. Together, this work provides support for and insights into a mechanism wherein TDG-mediated processes (e.g., DNA demethylation) are regulated through the direct interactions of TDG with RNA.


Asunto(s)
Timina ADN Glicosilasa , Timina ADN Glicosilasa/genética , Timina ADN Glicosilasa/metabolismo , Reparación del ADN , ADN/metabolismo , ARN , Proteínas de Unión al ARN/metabolismo , Timina
2.
Linacre Q ; 84(1): 57-73, 2017 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-28392599

RESUMEN

There is an urgent need to promote healthcare justice for patients as well as members of the healthcare team including physicians. In this article, we explain how principles of Catholic social teaching (i.e., dignity of the individual, common good, destination of goods, solidarity, and subsidiarity) are applied to health care, by featuring various types of outpatient clinics including free, charitable-direct primary care, hybrid, federally qualified health center, and rural health clinic. We describe how attempts have been made to improve the quality and access of health care by creating new medical schools (i.e., Marian University College of Osteopathic Medicine) and training programs as well as allocating government funding to alleviate the cost of training new healthcare providers through the National Health Service Corps. Finally, we suggest a few approaches (i.e., adopting new clinic models to include volunteer healthcare professionals and cross-training members of the healthcare team) to fill in current gaps in health care. Summary : There is a need to promote justice in healthcare. In this article, we explain how principles of Catholic social teaching are applied to health care. To illustrate this, we feature various types of outpatient clinics. We also describe how attempts have been made to improve the quality and access of health care. Finally, we suggest further ways to improve healthcare reform based upon Catholic social teaching.

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