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Telomeres are a significant challenge to DNA replication and are prone to replication stress and telomere fragility. The shelterin component TRF1 facilitates telomere replication but the molecular mechanism remains uncertain. By interrogating the proteomic composition of telomeres, we show that mouse telomeres lacking TRF1 undergo protein composition reorganisation associated with the recruitment of DNA damage response and chromatin remodellers. Surprisingly, mTRF1 suppresses the accumulation of promyelocytic leukemia (PML) protein, BRCA1 and the SMC5/6 complex at telomeres, which is associated with increased Homologous Recombination (HR) and TERRA transcription. We uncovered a previously unappreciated role for mTRF1 in the suppression of telomere recombination, dependent on SMC5 and also POLD3 dependent Break Induced Replication at telomeres. We propose that TRF1 facilitates S-phase telomeric DNA synthesis to prevent illegitimate mitotic DNA recombination and chromatin rearrangement.
This article was published in the following journal.
Chromatin domains and their associated structures must be faithfully inherited through cellular division to maintain cellular identity. However, accessing the localized strategies preserving chromatin...
Identifying proteins that function at replication forks is essential to understanding DNA replication, chromatin assembly, and replication-coupled DNA repair mechanisms. Combining quantitative mass sp...
Replication stress poses a serious threat to genome stability. Recombination-Dependent-Replication (RDR) promotes DNA synthesis resumption from arrested forks. Despite the identification of chromatin ...
DNA-replication machinery introduces intertwining and supercoiling of DNA strands as it traverses the double helix, which could impede replication and compromise genome stability. A new study in Cell ...
The Hippo signaling pathway regulates tissue growth and organ development in many animals, including humans. Pathway activity leads to inactivation of Yorkie, a transcriptional co-activator that drive...
The current study analyses the LV geometry of failing LVs measured by MRI scanning with respect to systolic versus diastolic function. A new surgical method for remodelling enlarged left v...
Purpose: Identification of the gene(s) involved in plasma membrane remodelling. Identification of the circulating markers affected by the defective membrane remodelling in a collection of ...
Severe asthma is a difficult to treat disease, characterized by bronchial remodelling, which is an abnormal repair process that contributes to the development of poorly reversible airway n...
Several studies have suggested that despite suppressive combination antiretroviral therapy (ART) in people who are HIV-positive, in some individuals there may be on-going viral replication...
This study will assess the relationship between collagen turnover, neurohormonal activation, scarring and left ventricle remodelling in patients 3 years following a myocardial infarction.
A single-stranded DNA-binding protein that is found in EUKARYOTIC CELLS. It is required for DNA REPLICATION; DNA REPAIR; and GENETIC RECOMBINATION.
A DNA-binding protein that mediates DNA REPAIR of double strand break, and GENETIC RECOMBINATION.
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).
In the interphase nucleus, a condensed mass of chromatin representing an inactivated X chromosome. Each X CHROMOSOME, in excess of one, forms sex chromatin (Barr body) in the mammalian nucleus. (from King & Stansfield, A Dictionary of Genetics, 4th ed)
An ATP-dependent DNA HELICASE that preferentially binds SINGLE-STRANDED DNA. It is a heterodimer consisting of an 80 kDa subunit (XRCC5) and 70 kDa subunit (XRCC6) that functions with DNA LIGASE IV in the repair of DOUBLE-STRANDED DNA BREAKS and V(D)J RECOMBINATION.
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...
Stress is caused by your perception of situations around you and then the reaction of your body to them. The automatic stress response to unexpected events is known as 'fight or flight'. Discovered by Walter Cannon in 1932, it is the release of h...