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In a process linked to DNA replication, duplicated chromosomes are entrapped in large, circular cohesin complexes and functional sister chromatid cohesion (SCC) is established by acetylation of the SMC3 cohesin subunit. Roberts Syndrome (RBS) and Warsaw Breakage Syndrome (WABS) are rare human developmental syndromes that are characterized by defective SCC. RBS is caused by mutations in the SMC3 acetyltransferase ESCO2, whereas mutations in the DNA helicase DDX11 lead to WABS. We found that WABS-derived cells predominantly rely on ESCO2, not ESCO1, for residual SCC, growth and survival. Reciprocally, RBS-derived cells depend on DDX11 to maintain low levels of SCC. Synthetic lethality between DDX11 and ESCO2 correlated with a prolonged delay in mitosis, and was rescued by knockdown of the cohesin remover WAPL. Rescue experiments using human or mouse cDNAs revealed that DDX11, ESCO1 and ESCO2 act on different but related aspects of SCC establishment. Furthermore, a DNA binding DDX11 mutant failed to correct SCC in WABS cells and DDX11 deficiency reduced replication fork speed. We propose that DDX11, ESCO1 and ESCO2 control different fractions of cohesin that are spatially and mechanistically separated.
This article was published in the following journal.
Name: PloS one
Chromosome instability (CIN), or continual changes in chromosome complements, is an enabling feature of cancer; however, the molecular determinants of CIN remain largely unknown. Emerging data now sug...
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 telo...
Bloom syndrome is characterized by severe pre- and postnatal growth deficiency, immune abnormalities, sensitivity to sunlight, insulin resistance, and a high risk for many cancers that occur at an ear...
Although the function of microtubules (MTs) in chromosome segregation during mitosis is well characterized, much less is known about the role of MTs on chromosomal functions during interphase. In the ...
Structural maintenance of chromosomes (SMC) complexes are key organizers of chromosome architecture in all kingdoms of life. Despite seemingly divergent functions, such as chromosome segregation, chro...
The major aim of this study is to test the effectiveness of a bundled, multi-level intervention (Sister to Sister) on smoking cessation outcomes in female smokers residing in public housin...
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...
Psychosocial and lifestyle stressors, such as job strain (JS) and marital factors have previously been associated with a sustained increase in blood pressure (BP). In a one-year longitudi...
COHESION is a randomized trial targeting reduction of systemic inflammation through an oral hygiene regimen incorporating a plaque-disclosing toothpaste and a control toothpaste.
The main purpose of this research is evaluate if HBMT reduces HAB in Soldiers, reduces intra-team conflict, improves trust, and improves unit cohesion. A secondary purpose of this research...
An exchange of segments between the sister chromatids of a chromosome, either between the sister chromatids of a meiotic tetrad or between the sister chromatids of a duplicated somatic chromosome. Its frequency is increased by ultraviolet and ionizing radiation and other mutagenic agents and is particularly high in BLOOM SYNDROME.
A DNA-dependent helicase and 3'-5' exonuclease. It has 3'->5' exonuclease activity towards double-stranded DNA with a 5'-overhang and binds preferentially to DNA substrates containing alternate secondary structures, such as replication forks and HOLLIDAY JUNCTIONS. Mutations in the WRN gene are associated with WERNER SYNDROME.
A DEAD box RNA helicase that contains two N-terminal CASPASE ACTIVATION AND RECRUITMENT DOMAINS. It functions as a sensor of viral NUCLEIC ACIDS such as DOUBLE-STRANDED RNA and activates the INNATE IMMUNE RESPONSE by inducing the expression of INTERFERON-ALPHA and INTERFERON-BETA. It may also regulate cell growth and APOPTOSIS.
A DEAD-box RNA helicase that contains an N-terminal DEATH-LIKE DOMAIN, AAA+ ATPase domain, and C-terminal RNA HELICASE activity. It functions as an innate immune receptor through its recognition of viral nucleic acids. It also induces the expression of INTERFERON TYPE I and proinflammatory CYTOKINES. Its ligands include: 5'-triphosphorylated SINGLE-STRANDED RNA, DOUBLE-STRANDED RNA (dsRNA), and short dsRNA (less than 1 kb in length).
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).
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...