Track topics on Twitter Track topics that are important to you
Alpha thalassemia/mental retardation syndrome X-linked (ATRX), a DAXX (death domain-associated protein)-associated chromatin remodeler, is often lost in cells using the alternative lengthening of telomeres (ALT) pathway, but it is not known how ATRX loss leads to ALT. We report that ATRX deletion from mouse cells altered the repair of telomeric double-strand breaks (DSBs) and induced ALT-like phenotypes, including ALT-associated promyelocytic leukemia (PML) bodies (APBs), telomere sister chromatid exchanges (T-SCEs), and extrachromosomal telomeric signals (ECTS). Mechanistically, we show that ATRX affects telomeric DSB repair by promoting cohesion of sister telomeres and that loss of ATRX in ALT cells results in diminished telomere cohesion. In addition, we document a role for DAXX in the repair of telomeric DSBs. Removal of telomeric cohesion in combination with DAXX deficiency recapitulates all telomeric DSB repair phenotypes associated with ATRX loss. The data reveal that ATRX has an effect on telomeric DSB repair and that this role involves both telomere cohesion and a DAXX-dependent pathway.
This article was published in the following journal.
Name: PLoS biology
Loss of the histone H3.3-specific chaperone component ATRX or its partner DAXX frequently occurs in human cancers that employ alternative lengthening of telomeres (ALT) for chromosomal end protection,...
The chromatin-remodeling complex ATRX/DAXX is one of the major epigenetic factors that controls heterochromatin maintenance due to its role in histone deposition. ATRX is involved in nucleosome config...
Molecular characterization of lung cancer specimens after radical surgery offers additional prognostic information and may help to guide adjuvant therapeutic procedures. The transcriptional regulators...
Fanconi anemia (FA) is a chromosome instability syndrome characterized by increased cancer predisposition. Specifically, the FA pathway functions to protect genome stability during DNA replication. Th...
DAXX displays complex biological functions. Remarkably, DAXX overexpression is a common feature in diverse cancers, which correlates with tumorigenesis, disease progression and treatment resistance. S...
The general hypothesis put forward in this study is that the degree of cohesion (agreement) in the relationship, or dyadic adjustment affects a patient's quality of life and clinical cours...
ATRX (X-linked mental retardation and alpha-thalassaemia syndrome protein) loss and pTERT (Telomerase reverse transcriptase) mutation are diagnostic markers of gliomas. However, 4 to 28% o...
This project explores the implication of the telomere pathway in ovarian premature and regular aging. Telomere length and maintenance underlie several biological processes such cancer, agi...
The purpose of this study is to determine and compare the possible affects of two different inguinal hernia repair technique (TEP and Lichtenstein) on serum ASA levels.
In this study, the characterization of human malignant glioma cell lines is described. After mechanical and enzymatic digestion of glioblastoma human biopsies from Neuromed IRCCS Neurosurg...
ATP-dependent DNA helicase that contains two N-terminal ZINC FINGERS and C-terminal ATP-binding and helicase domains. It functions in the regulation of gene transcription and CHROMATIN REMODELING. ATRX undergoes cell-cycle dependent phosphorylation, which causes it to translocate from the NUCLEAR MATRIX to CHROMATIN; thus, it may change its role from gene regulation during INTERPHASE to ensuring proper chromosome segregation at MITOSIS. Mutations in the ATRX gene are associated with cases of X-LINKED MENTAL RETARDATION co-morbid with ALPHA-THALASSEMIA (ATRX syndrome).
A ubiquitously expressed telomere-binding protein that is present at TELOMERES throughout the cell cycle. It is a suppressor of telomere elongation and may be involved in stabilization of telomere length. It is structurally different from TELOMERIC REPEAT BINDING PROTEIN 1 in that it contains basic N-terminal amino acid residues.
A ubiquitously expressed telomere-binding protein that is present at TELOMERES throughout the CELL CYCLE. It is a suppressor of telomere elongation and may be involved in stabilization of telomere length. It is structurally different from TELOMERIC REPEAT BINDING PROTEIN 2 in that it contains acidic N-terminal amino acid residues.
The reconstruction of a continuous two-stranded DNA molecule without mismatch from a molecule which contained damaged regions. The major repair mechanisms are excision repair, in which defective regions in one strand are excised and resynthesized using the complementary base pairing information in the intact strand; photoreactivation repair, in which the lethal and mutagenic effects of ultraviolet light are eliminated; and post-replication repair, in which the primary lesions are not repaired, but the gaps in one daughter duplex are filled in by incorporation of portions of the other (undamaged) daughter duplex. Excision repair and post-replication repair are sometimes referred to as "dark repair" because they do not require light.
Highly conserved proteins that specifically bind to and activate the anaphase-promoting complex-cyclosome, promoting ubiquitination and proteolysis of cell-cycle-regulatory proteins. Cdc20 is essential for anaphase-promoting complex activity, initiation of anaphase, and cyclin proteolysis during mitosis.
Within medicine, nutrition (the study of food and the effect of its components on the body) has many different roles. Appropriate nutrition can help prevent certain diseases, or treat others. In critically ill patients, artificial feeding by tubes need t...