GENOMIC PLASTICITY IN THE HUMAN U2 SNRNA GENE CLUSTER

描述：（改编自应用程序。）编码U2的基因 小核RNA（snRNA）以5至>22个完美串联阵列存在 人染色体17 q21上的5.8 KB重复单位的拷贝数。该基因座 是一个脆弱的网站，这可能是由腺病毒12感染。 此外，该基因座已在其目前的位置保持了> 3500万年 通过灵长类动物谱系中的多次物种形成事件。的 首席研究员提出了一个多方面的方法来理解 腺病毒诱导的染色体脆性。六个具体目标包括： (1)脆性位点诱导所需的U2染色体序列将 （2）染色体的功能需要鉴定和分析; 将确定腺病毒12的脆弱性，包括以下要求： snRNA转录，染色质结构，甲基化，拓扑异构酶 绑定，以及复制的起源和调度;（3） 需要高浓度的转录单位， （4）确定是否存在脆性位点; 这个灵长类基因座的历史将被追溯。DNA测序从一个 各种灵长类动物，以及人类群体，将进行， 比较和研究遗传和连锁机制;（5） U2重复序列对速率、边界和稳定性的影响 将研究基因扩增;和（6）域和 腺病毒12 E1 B 55 kDa蛋白的功能， 将表征诱导染色体脆性。

DESCRIPTION: (Adapted from the application.) The genes encoding U2 small nuclear RNA (snRNA) exist as a perfect tandem array of 5 to >22 copies of a 5.8 KB repeat unit on human chromosome 17q21. This locus is a fragile site which may be induced by adenovirus 12 infection. Further, the locus has been maintained at its present site for >35 Myr through multiple speciation events in the primate lineage. The Principal Investigator proposes a multi-faceted approach to understanding adenovirus-induced chromosome fragility. Six specific aims include: (1) U2 chromosomal sequences required for fragile site induction will be identified and analyzed; (2) The chromosomal functions required for adeno 12 virus fragility will be identified, including requirements for snRNA transcription, chromatin structure, methylation, topoisomerase binding, and the origin and scheduling of replication; (3) The requirement for a high concentration of transcription units for the existence of a fragile site will be determined; (4) The evolutionary history of this primate locus will be traced. DNA sequencing from a variety of primates, as well as human groups, will be performed to compare and investigate mechanisms of inheritance and linkage; (5) The influence of U2 repeat sequences on the rate, boundaries, and stability of gene amplification will be investigated; and (6) The domains and functions of the adenovirus 12 E1B 55 kDa protein which are required for inducing chromosome fragility will be characterized.