AI Article Synopsis
Article Abstract
The , , and genes encode for the nuclear MRN protein complex, which senses the DNA double strand breaks and initiates the DNA repair. The MRN complex also participates in the activation of ATM kinase, which coordinates DNA repair with the p53-dependent cell cycle checkpoint arrest. Carriers of homozygous germline pathogenic variants in the MRN complex genes or compound heterozygotes develop phenotypically distinct rare autosomal recessive syndromes characterized by chromosomal instability and neurological symptoms. Heterozygous germline alterations in the MRN complex genes have been associated with a poorly-specified predisposition to various cancer types. Somatic alterations in the MRN complex genes may represent valuable predictive and prognostic biomarkers in cancer patients. MRN complex genes have been targeted in several next-generation sequencing panels for cancer and neurological disorders, but interpretation of the identified alterations is challenging due to the complexity of MRN complex function in the DNA damage response. In this review, we outline the structural characteristics of the MRE11, RAD50 and NBN proteins, the assembly and functions of the MRN complex from the perspective of clinical interpretation of germline and somatic alterations in the , and genes.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10051278 | PMC |
| http://dx.doi.org/10.3390/ijms24065612 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Interaction of DDB1 with NBS1 in a DNA Damage Checkpoint Pathway.
Int 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 PDFPhosphorylation of 'SDT-like' motifs in ATRX mediates its interaction with the MRN complex and is important for ALT pathway suppression.
Open 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.
View Article and Find Full Text PDFMulti-target therapeutic modulation with natural compounds towards DNA repair MRN-checkpoint sensor genes (MRN-CSGs) and oncogenic miRNAs in breast cancer patients: a Clinico-Informatic study.
Integr Biol (Camb)
January 2024
Department of Biophysics, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh 160012India.
Breast cancer, more prevalent in women, often arises due to abnormalities in the MRN-checkpoint sensor genes (MRN-CSG), responsible for DNA damage detection and repair. Abnormality in this complex is due to the suppression of various effectors such as siRNAs, miRNAs, and transcriptional factors responsible for breast tumor progression. This study analyzed breast tumor samples (n = 60) and identified four common miRNAs (miR-1-3p, miR-210-3p, miR-16-5p, miR-34a-5p) out of 12, exploring their interactions with MRN-CSG.
View Article and Find Full Text PDFRAD51 recombinase and its paralogs: Orchestrating homologous recombination and unforeseen functions in protozoan parasites.
Exp Parasitol
December 2024
Posgrado en Ciencias Genómicas, Universidad Autónoma de la Ciudad de México (UACM), San Lorenzo #290, Col. Del Valle, CP 03100, Mexico City, Mexico. Electronic address:
The DNA of protozoan parasites is highly susceptible to damage, either induced by environmental agents or spontaneously generated during cellular metabolism through reactive oxygen species (ROS). Certain phases of the cell cycle, such as meiotic recombination, and external factors like ionizing radiation (IR), ultraviolet light (UV), or chemical genotoxic agents further increase this susceptibility. Among the various types of DNA damage, double-stranded breaks (DSBs) are the most critical, as they are challenging to repair and can result in genetic instability or cell death.
View Article and Find Full Text PDFS6K1 Controls DNA Damage Signaling Modulated by the MRN Complex to Induce Radioresistance in Lung Cancer.
Int J Mol Sci
September 2024
Department of Radiation Oncology, Sidney Kimmel Comprehensive Cancer Center, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Radiation is a mainstay of lung cancer treatment; however, resistance frequently develops. Identifying novel therapeutic targets to increase radiation sensitivity is crucial. S6K1 is a serine/threonine kinase known to regulate protein translation which is associated with radioresistance, but the mechanisms involved are unknown.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!