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Full-Text Articles in Bioinformatics
B Cell Acute Lymphoblastic Leukemia Is Driven By Activating Janus Kinase Mutations Cooperating With Spi1 And Spib Deletions In A Murine Model, Michelle Lim
Electronic Thesis and Dissertation Repository
B cell acute lymphoblastic leukemia (B-ALL) is caused by genetic lesions in developing B cells that function as drivers for accumulation of additional mutations in an evolutionary selection process. We investigated secondary drivers of leukemogenesis and their mechanism(s) of arising in a mouse model of B-ALL driven by PU.1/Spi-B deletion (Mb1-CreDPB). Whole exome sequencing revealed recurrent mutations in Jak3 (encoding Janus Kinase 3) and Jak1. Mutations with high variant allele frequency (VAF) were dominated by C->T transition mutations that were compatible with AID, whereas the majority of mutations, with low VAF, were dominated by C->A transversions associated with …
The Role Of Thymine-Dna Glycosylase In Transcriptional Regulation, Bart Kolendowski
The Role Of Thymine-Dna Glycosylase In Transcriptional Regulation, Bart Kolendowski
Electronic Thesis and Dissertation Repository
Precise control over transcriptional regulation is required for normal cell function. Errors in transcriptional regulation underpin many diseases including cancer. Thymine DNA Glycosylase (TDG) is a base excision repair protein and a coregulator that has been implicated in a diverse set of fundamental biological processes including embryonic development, nuclear receptor signaling and Wnt signaling. Importantly, TDG has been shown to play an important role in transcriptional regulation in a wide variety of systems. Details surrounding the mechanism through which TDG acts remain unclear. In this thesis we explore the role of TDG in Estrogen Receptor (ER)-dependent signaling and in cellular …