Examining the Role of Msh2 and Mre11 in Telomere Rescue
Abstract
Tumorigenesis is characterized by genome instability that results in genetic changes that promote a cancerous state I. Instability at telomeres can result in uncapping" of the ends of linear chrnmosomes, making them vulnerable to recombination, mutation and gross-chromosomal rearrangement (GCR)2,3,4. Continuously dividing human somatic cells and S. cerevisiae cells lacking functional telomerase, a ribonucleoprotein complex required for telomere replication, experience progressive telomere degradation that culminates in replicative senescence 5,6. Our research has shown that during replicative senescence genes located proximal to telomeres experience increases in mutationand GCR that are dependent on the error- prone polymerase genes REVi and REV7. Interestingly, viability is increased and replicative senescence is delayed in telomerase deficient diploid cells. This may be because the presence of a homologous chromosome provides the opportunity to rescue defective chromosomes by inter-homolog exchange (IHE), or to tolerate their loss. In support of this idea both IHE and chromosome loss (CL) increase during replicative senescence. Senescence-associated IHE is dependent on the central homologous recombination gene, RAD52, but is independent from the error-prone polymerase genes REV1 and REV7. Finally, we have identified a new role for telomerase in facilitating the formation of translocations after double-strand breaks are made on two different chromosomes.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2007
- Accession Number
- ADA469755
Entities
People
- Damon Meyer