Examining the Role of Mah2 and Mrell in Telomere Rescue
Abstract
Interestingly, about 155 of human cancers have an inactive telomerase gene, leading to the discovery of telomerase-independent mechanisms for regaining telomeric sequences by homologous recombination referred to as alternative lengthening of telomeres(ALT). In S. cerevisiae, there are two ALT pathways controlled by Rad51 and Mre11/Rad50/Xrs2(MRX). The ALT pathway used in humans generates telomeres that resemble the MRX-dependent survivors found in yeast. Recent evidence suggests that the mismatch repair pathway, which is thought to block recombination between mismatched telomeric sequences, limits ALT, perhaps by opposing MRX-dependent ALT. I propose to examine the role of Msh2, the central mismatch repair protein, in restricting ALT in S. cerevisiae. Particular attention will be paid to whether Rad51 or MRX pathway recombinations predominate in these strains, suggesting that mismatch repair selectively restricts one pathway or the other. In addition, the role of Mre11 in ALT will be studied by determining the effect of mutations in specific functional domains of Mre11 in telomerase-independent telomere rescue. This may help determine the relationship between MRX-dependent ALT and specific homologus recombination mechanisms.
Document Details
- Document Type
- Technical Report
- Publication Date
- Apr 01, 2005
- Accession Number
- ADA434791
Entities
People
- Damon Meyer