The splicing inhibitor Isoginkgetin leads to defects in multiple phases of the cell cycle

Isoginkgetin is a naturally occurring compound from Ginkgo biloba trees that has anti-neoplastic activities related to inhibition of spliceosome assembly. The p53-tumour suppressor plays a prominent role in ell G1 and G2 cycle checkpoints and p53 is strongly activated in response to transcriptional stresses. Therefore, we determined the effect of p53 and Isoginkgetin treatment on cell cycle progression. Wildtype p53 expressing cells exhibited a remarkable S phase defect while the p53-null subline accumulated with 4C DNA content. Despite the pronounced difference in these isogenic strains, there was no pronounced p53 transcriptional response as assessed by qRT-PCR and preliminary microarray analysis. Instead, Isoginkgetin leads to altered pre-mRNA splicing of S and M phase-specific transcripts. These results suggest that cell cycle alterations are the direct result of abnormal splicing of cell cycle regulatory mRNAs and not p53 dependent checkpoints.

Name thesis:degree_name

Master of Science (M.Sc.)

Level thesis:degree_level

Master's

Discipline thesis:degree_discipline

Biology

Grantor dc:publisher

Carleton University

Year dc:date.issued

2016

Author dc:creator

• Rick, Kayleigh R. C. (Ruth Christel)

Statement dc:rights

• Copyright © 2016 the author(s). Theses may be used for non-commercial research, educational, or related academic purposes only. Such uses include personal study, research, scholarship, and teaching. Theses may only be shared by linking to Carleton University Institutional Repository and no part may be used without proper attribution to the author. No part may be used for commercial purposes directly or indirectly via a for-profit platform; no adaptation or derivative works are permitted without consent from the copyright owner.

Language dc:language.iso

en

DOI

10.22215/etd/2016-11501

OAI identifier oai:identifier

oai:carleton.scholaris.ca:20.500.14718/38875