Functional analysis of ISWI complexes in mammalian cells.
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Adenosine Triphosphatases↗
Biomedical subjects
Nadine Collins
Publications and source records attributed to Nadine Collins.
Molecular diagnostics in routine practice: quality issues and application to complex disease.
The public already has concerns about 'the new genetics', and it is clear that confidence can only be maintained by scrupulous attention to quality. Standards can be improved by harmonization of methods, discouraging poor practice and using appropriate internal and external quality controls. At present, despite the profound implications of genetic test results, few genetic tests are subject to sufficient scrutiny. The Human Genome Project will lead to the identification of numerous genetic variations contributing to multifactorial diseases, and high-throughput technologies will permit the generation of disease-susceptibility profiles. Clinical laboratories will need to develop the wherewithal to handle these data and present them in a format that is clinically useful.
Biotechnology↗
An ACF1-ISWI chromatin-remodeling complex is required for DNA replication through heterochromatin.
The mechanism by which the eukaryotic DNA-replication machinery penetrates condensed chromatin structures to replicate the underlying DNA is poorly understood. Here we provide evidence that an ACF1-ISWI chromatin-remodeling complex is required for replication through heterochromatin in mammalian cells. ACF1 (ATP-utilizing chromatin assembly and remodeling factor 1) and an ISWI isoform, SNF2H (sucrose nonfermenting-2 homolog), become specifically enriched in replicating pericentromeric heterochromatin. RNAi-mediated depletion of ACF1 specifically impairs the replication of pericentromeric heterochromatin. Accordingly, depletion of ACF1 causes a delay in cell-cycle progression through the late stages of S phase. In vivo depletion of SNF2H slows the progression of DNA replication throughout S phase, indicating a functional overlap with ACF1. Decondensing the heterochromatin with 5-aza-2-deoxycytidine reverses the effects of ACF1 and SNF2H depletion. Expression of an ACF1 mutant that cannot interact with SNF2H also interferes with replication of condensed chromatin. Our data suggest that an ACF1-SNF2H complex is part of a dedicated mechanism that enables DNA replication through highly condensed regions of chromatin.
3T3 Cells↗