Date of Graduation
12-2010
Document Type
Dissertation (PhD)
Program Affiliation
Biomedical Sciences
Degree Name
Doctor of Philosophy (PhD)
Advisor/Committee Chair
Dr. Lei Li
Committee Member
Dr. Andreas Bergmann
Committee Member
Dr. Randy J. Legerski
Committee Member
Dr. Mong-Hong Lee
Committee Member
Dr. Guillermina Lozano
Abstract
RMI1 (BLM-Associated Protein 75 or Blap75) is highly conserved from yeast to human. Previous studies have shown that hRMI1 is required for BLM/TopoIIIα/RMI1 complex stability and function. However, in vivo functions of RMI1 remain elusive. To address this question, I generated RMI1 knockout mice by homologous replacement targeting. While RMI1+/- mice showed no obvious phenotype, deletion of both RMI1 alleles leads to early embryonic lethality before implantation. I then generated RMI1/p53 double knockout mice. After ionizing radiation treatment at 4Gy, RMI1/p53 double-heterzygous mice showed shortened tumor latency and aggressive tumor types when comparing with wild type, RMI1+/- and p53+/- control cohorts. My study suggests a dual-functional role of RMI1 in early embryonic development and tumor suppression.
Keywords
RMI1, HR, DSB.