Werner syndrome (WS) is a recessive inherited human disease characterized by the early onset of aging. The gene mutated in WS encodes a DNA helicase that unwinds the double helical structure of DNA in the 3'-->5' direction as well as a 3'-->5' exonuclease. Our previous studies indicated that the activity of Werner syndrome helicase (WRN) could be stimulated by human replication protein A (hRPA), a heterotrimeric single-stranded DNA binding protein. We now localize the interaction between WRN and hRPA by measuring the stimulation of helicase activity and the binding of WRN by hRPA and its derivatives. The large subunit of hRPA (hRPA70) stimulates WRN helicase to the same extent as the hRPA heterotrimer, whereas the dimer of the two smaller subunits (hRPA 32.14) does not stimulate. By examining hRPA70 mutants with progressive deletions from either the C- or N-terminus, we found that the domain responsible for stimulation lies in the N-terminal half of the protein. By using enzyme-linked immunosorbent assay (ELISA) to examine physical interaction between WRN and the same deletion mutants, we found that the WRN-binding motif is located within amino acids 100-300 and overlaps with the single-stranded DNA binding domain (amino acids 150-450). We suggest that hRPA, by engaging in both protein-protein and protein-DNA interactions, facilitates unwinding events catalyzed by WRN helicase during DNA synthetic processes. These data should help further elucidation of the molecular mechanisms of genetic instability and premature aging phenotypes manifested by WS.
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http://dx.doi.org/10.1016/s0047-6374(03)00164-7 | DOI Listing |
Adv Sci (Weinh)
December 2024
School of Pharmaceutical Sciences, Guangzhou University of Chinese Medicine, Guangzhou, 510006, China.
DNA helicases play a pivotal role in maintaining genome integrity by unwinding the DNA double helix and are often considered promising targets for drug development. However, assessing specific DNA helicase activity in living cells remains challenging. Herein, the first anchor-embedded duplex (ATED) probe, 17GC, is constructed to uniquely monitor the unwinding activity of Werner syndrome helicase (WRN), a clinical anticancer target.
View Article and Find Full Text PDFLancet Reg Health Eur
February 2025
Department of Cardiology, University Heart and Vascular Center Hamburg, Hamburg, Germany.
Background: Frailty is a significant predictor for adverse outcomes. Yet, data on prevalence and treatment of frail patients with acute coronary syndrome (ACS) remains limited. We aimed to investigate frailty prevalence, interventional treatment frequency, and in-hospital outcome for all patients hospitalized for ACS in Germany from 2005 to 2022 and validate the Hospital Frailty Risk Score (HFRS) in this population.
View Article and Find Full Text PDFBackground: Complete bicorporeal uterus, double cervix and obstructive longitudinal vaginal septum (classified as U3bC2V2 according to ESHRE/ESGE classification) is a rare congenital anomaly of the genital tract. This condition is typically associated with ipsilateral renal agenesis and is known as Herlyn-Werner-Wunderlich syndrome or OHVIRA (Obstructed HemiVagina and Ipsilateral Renal Anomaly) syndrome. The primary symptoms include dysmenorrhea and pelvic pain, which usually manifest after menarche due to haematocolpos in the obstructed hemivagina.
View Article and Find Full Text PDFJ Clin Med
November 2024
Department of Pediatric Cardiology and General Pediatrics, Medical University of Warsaw, 02-091 Warsaw, Poland.
The goal of this study was to assess if body mass index (BMI) affects the pace of cardiac muscle recovery in children after Pediatric Inflammatory Multisystem Syndrome Temporally Associated with SARS-CoV-2/COVID-19 (PIMS-TS). A prospective single-center study enrolled consecutive children hospitalized with PIMS-TS between October 2020 and February 2022 and followed up after 6 weeks and 6 months. In all children, three-dimensional echocardiography and global longitudinal strain were used to assess ventricular function and the results were analyzed according to patients' BMI status.
View Article and Find Full Text PDFJ Clin Med
November 2024
Department of Obstetrics and Gynecology, Maastricht University Medical Centre, 6229 HX Maastricht, The Netherlands.
(1) : The worldwide endometrial cancer (EC) incidence is rising, amongst others linked to obesity, type 2 diabetes mellitus (T2DM), and metabolic syndrome, possibly due to low-grade adipose tissue inflammation. We studied immune cell infiltration in the endometrium in relation to diagnosis and obesity. (2) : A cohort was created ( = 44) from postmenopausal women, lean ( = 15) and obese ( = 29), with bleeding complaints due to EC ( = 18) or benign pathology ( = 26).
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