In eukaryotic cells, DNA transactions such as replication, repair, and transcription require a large set of proteins. In all of these events, complexes of more than 30 polypetides appear to function in highly organized and structurally well-defined machines. We have learned in the past few years that the three essential macromolecular events, replication, repair, and transcription, have common functional entities and are coordinated by complex regulatory mechanisms. This can be documented for replication and repair, for replication and checkpoint control, and for replication and cell cycle control, as well as for replication and transcription. In this review we cover the three different protein classes: DNA polymerases, DNA polymerase accessory proteins, and selected transcription factors. The "common enzyme-different pathway strategy" is fascinating from several points of view: first, it might guarantee that these events are coordinated; second, it can be viewed from an evolutionary angle; and third, this strategy might provide cells with backup mechanisms for essential physiological tasks.
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http://dx.doi.org/10.1016/s0079-6603(00)65007-9 | DOI Listing |
Arthrosc Tech
December 2024
Dr. Pimprikar's ADTOOS Clinics, Nashik, India.
Avulsion of the triceps tendon is a rare injury accounting for less than 1% of all tendon injuries. The triceps is an extensor of the elbow and causes compromised function if left untreated. Complete ruptures should be treated with early repairs for satisfactory outcomes.
View Article and Find Full Text PDFJTCVS Open
December 2024
Division of Pediatric Cardiac Surgery, Department of Cardiothoracic Surgery, Stanford University, Palo Alto, Calif.
Objective: The study objective was to investigate the effect of free-edge length on valve performance in bicuspidization repair of congenitally diseased aortic valves.
Methods: In addition to a constructed unicuspid aortic valve disease model, 3 representative groups-free-edge length to aortic diameter ratio 1.2, 1.
Commun Med (Lond)
January 2025
Eshelman School of Pharmacy, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.
Background: Gene signatures derived from transcriptomic-causal networks offer potential for tailoring clinical care in cancer treatment by identifying predictive and prognostic biomarkers. This study aimed to uncover such signatures in metastatic colorectal cancer (CRC) patients to aid treatment decisions.
Methods: We constructed transcriptomic-causal networks and integrated gene interconnectivity into overall survival (OS) analysis to control for confounding genes.
Nature
January 2025
Stanford Cancer Institute, School of Medicine, Stanford University, Stanford, CA, USA.
Breast cancer is a highly heterogeneous disease whose prognosis and treatment as defined by the expression of three receptors-oestrogen receptor (ER), progesterone receptor and human epidermal growth factor receptor 2 (HER2; encoded by ERBB2)-is insufficient to capture the full spectrum of clinical outcomes and therapeutic vulnerabilities. Previously, we demonstrated that transcriptional and genomic profiles define eleven integrative subtypes with distinct clinical outcomes, including four ER subtypes with increased risk of relapse decades after diagnosis. Here, to determine whether these subtypes reflect distinct evolutionary histories, interactions with the immune system and pathway dependencies, we established a meta-cohort of 1,828 breast tumours spanning pre-invasive, primary invasive and metastatic disease with whole-genome and transcriptome sequencing.
View Article and Find Full Text PDFCurr Cancer Drug Targets
January 2025
Cancer Research Center, Shantou University Medical College, Shantou 515041, Guangdong, PR China.
Among the Poly(ADP-ribose) Polymerase (PARP) family in mammals, PARP1 is the first identified and well-studied member that plays a critical role in DNA damage repair and has been proven to be an effective target for cancer therapy. Here, we have reviewed not only the role of PARP1 in different DNA damage repair pathways, but also the working mechanisms of several PARP inhibitors (PARPi), inhibiting Poly-ADP-ribosylation (PARylation) processing and PAR chains production to trap PARP1 on impaired DNA and inducing Transcription- replication Conflicts (TRCs) by inhibiting the PARP1 activity. This review has systematically summarized the latest clinical application of six authorized PARPi, including olaparib, rucaparib, niraparib, talazoparib, fuzuloparib and pamiparib, in monotherapy and combination therapies with chemotherapy, radiotherapy, and immunotherapy, in different kinds of cancer.
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