GENOMIC PLASTICITY IN THE HUMAN U2 SNRNA GENE CLUSTER

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DESCRIPTION : There are several goals related to chromosome structure and function in the area of repeated active genes, in particular the genes for snRNA U2 and snRNA U1. The observation that Adenovirus12 E1B 55KD protein can cause fragility in the chromosome at the U2 and U1 sites but only in the presence of an active p53 gene product. They will define the regions and functions of p53 that are required for fragility. They will define the regions of the 55KD protein required for p53 induction of fragility. They will try to identify the regions of p53 and 55KD that may interact with each other. To follow up their observation that Cockayne syndrome complementation group B (CSB) induces fragility in the same regions they will determine which portions of this large protein can rescue normal chromosome condensation. They will develop negative CSB mutants and examine the chromosome of the U2 locus in interphase and metaphase and in the fragile states induced by the CSB mutation Finally, will determine whether CSB induced fragility requires p53. They have evidence that stabilization of large tandem arrays of functional U2 genes requires a CT70 microsatellite. They will determine whether this enhancement of stability is specific for UsnRNA promoters and whether the chromatin structure of the CT repeat depends on active U2 transcription. Finally, they have found that the coiled bodies (CB) associate preferentially with U1 and U2 gene clusters. They will ask whether the association of CBs with the U2 gene cluster requires snRNA transcription, an active UsnRNA coding region, or snRNP protein binding sites on the nacent or newly released UsnRNA.