Genomes are subject to constant threat by damaging agents that generate DNA double-strand breaks (DSBs). The ends of linear chromosomes need to be protected from DNA damage recognition and end-joining, and this is achieved through protein-DNA complexes known as telomeres. The Mre11-Rad50-Nbs1 (MRN) complex plays important roles in detection and signaling of DSBs, as well as the repair pathways of homologous recombination (HR) and non-homologous end-joining (NHEJ). In addition, MRN associates with telomeres and contributes to their maintenance. Here, we provide an overview of MRN functions at DSBs, and examine its roles in telomere maintenance and dysfunction.
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http://dx.doi.org/10.1016/j.febslet.2010.07.029 | DOI Listing |
Cancer Diagn Progn
January 2025
Department of General Surgical Science, Graduate School of Medicine, Gunma University, Maebashi, Japan.
Background/aim: Karyopherin alpha 2 (KPNA2) has been reported to be associated with cancer aggressiveness and treatment resistance via transporting several cargo proteins into the nucleus, such as cancer-promoting E2F and DNA repair-related MRN complex. Recent studies have highlighted the KPNA2 functions in tumorigenesis and the progression of various cancers. However, the importance of KPNA2 expression has yet to be elucidated in clinical neuroblastoma patients.
View Article and Find Full Text PDFPLoS Pathog
January 2025
State Key Laboratory of Virology and Biosafety and Hubei Province Key Laboratory of Allergy and Immunology, Institute of Medical Virology, TaiKang Medical School, Wuhan University, Wuhan, China.
Chronic hepatitis B virus (HBV) infection can significantly increase the incidence of cirrhosis and liver cancer, and there is no curative treatment. The persistence of HBV covalently closed circular DNA (cccDNA) is the major obstacle of antiviral treatments. cccDNA is formed through repairing viral partially double-stranded relaxed circular DNA (rcDNA) by varies host factors.
View Article and Find Full Text PDFCurr J Neurol
April 2024
Iranian Center of Neurological Research, Neuroscience Institute, Tehran University of Medical Sciences, Tehran, Iran.
Carpal tunnel syndrome (CTS) is a common peripheral nerve entrapment disorder that is diagnosed using clinical signs and symptoms and confirmed via nerve conduction studies (NCSs). While NCS is a semi-invasive procedure, magnetic resonance imaging (MRI) is a non-invasive diagnostic tool that detects macroscopic nerve abnormalities and evaluates a patient's surgical or medication treatment options. This study assessed magnetic resonance neurography (MRN)'s diagnostic and grading value by comparing it to electrodiagnostic studies in patients with CTS and healthy individuals.
View Article and Find Full Text PDFInt J Mol Sci
December 2024
Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University, Seoul 06351, Republic of Korea.
Various DNA damage checkpoint control mechanisms in eukaryotic cells help maintain genomic integrity. Among these, NBS1, a key component of the MRE11-RAD50-NBS1 (MRN) complex, is an essential protein involved in the DNA damage response (DDR). In this study, we discovered that DNA damage-binding protein 1 (DDB1) interacts with NBS1.
View Article and Find Full Text PDFOpen Biol
December 2024
Department of Oncology, University of Oxford, Oxford OX3 7DQ, UK.
Approximately 10-15% of human cancers are telomerase-negative and maintain their telomeres through a recombination-based process known as the alternative lengthening of telomeres (ALT) pathway. Loss of the alpha-thalassemia/mental retardation, X-linked (ATRX) chromatin remodeller is a common event in ALT-positive cancers, but is generally insufficient to drive ALT induction in isolation. We previously demonstrated that ATRX binds to the MRN complex, which is also known to be important in the ALT pathway, but the molecular basis of this interaction remained elusive.
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