Poly(ADP-ribose) polymerases (PARPs) regulate the function of target proteins by modifying them with ADP-ribose, a large and unique post-translational modification. Humans express 17 PARPs; however, historically, much of the focus has been on PARP1 and its function in DNA damage repair. Recent work has uncovered an amazing diversity of function for these enzymes including the regulation of fundamental physiological processes in the cell and at the organismal level, as well as new roles in regulating cellular stress responses. In this review, we discuss recent advancements in our understanding of this important protein family, and technological developments that have been critical for moving the field forward. Finally, we discuss new directions that we feel are important areas of further scientific exploration.
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http://dx.doi.org/10.1111/febs.13737 | DOI Listing |
Apoptosis
April 2023
Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, School of Medicine, Northwest University, Taibai North Road 229, Xi'an, 710069, Shaanxi, China.
The normal colorectal mucosa undergoes precancerous lesions that can develop over time into colorectal cancer (CRC). In the stage of precancerous lesions, DNA replication stress may lead to genome instability. We have performed whole-exome sequencing on genomic DNA obtained from three cases of CRC tissues and identified a novel frameshift mutation of DNA damage inducible 1 homolog 2 gene (DDI2, c.
View Article and Find Full Text PDFFront Physiol
December 2019
Department of Clinical and Molecular Sciences (DISCLIMO), Università Politecnica delle Marche, Ancona, Italy.
Despite the decline in their proliferative potential, senescent cells display a high metabolic activity. Senescent cells have been shown to acquire a more glycolytic state even in presence of high oxygen levels, in a way similar to cancer cells. The diversion of pyruvate, the final product of glycolysis, away from oxidative phosphorylation results in an altered bioenergetic state and may occur as a response to the enhanced oxidative stress caused by the accumulation of dysfunctional mitochondria.
View Article and Find Full Text PDFNature
April 2019
Department of Molecular, Cell and Cancer Biology, University of Massachusetts Medical School, Worcester, MA, USA.
Current programmable nuclease-based methods (for example, CRISPR-Cas9) for the precise correction of a disease-causing genetic mutation harness the homology-directed repair pathway. However, this repair process requires the co-delivery of an exogenous DNA donor to recode the sequence and can be inefficient in many cell types. Here we show that disease-causing frameshift mutations that result from microduplications can be efficiently reverted to the wild-type sequence simply by generating a DNA double-stranded break near the centre of the duplication.
View Article and Find Full Text PDFPLoS One
February 2015
Department of Medicine, Knapp Center for Biomedical Discovery, University of Chicago, Chicago, Illinois, United States of America.
The Japanese traditional medicine daikenchuto (TU-100) has anti-inflammatory activities, but the mechanisms remain incompletely understood. TU-100 includes ginger, ginseng, and Japanese pepper, each component possessing bioactive properties. The effects of TU-100 and individual components were investigated in a model of intestinal T lymphocyte activation using anti-CD3 antibody.
View Article and Find Full Text PDFBreast Cancer Res
April 2011
Department of Pathology, Singapore General Hospital, Outram Road, Singapore 169608, Singapore.
Introduction: Triple negative breast cancer is associated with poorer prognosis and unresponsiveness to endocrine and anti-HER2 directed agents. Despite emerging data supporting the use of polyADP-ribose polymerase (PARP) inhibitors, complete and durable responses are rare and exploration of additional targeted therapies is needed. Epidermal growth factor receptor (EGFR) is expressed in triple negative breast cancer and several clinical trials are testing the role of anti-EGFR directed therapy.
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