YEAST 2017

28th International Conference on Yeast Genetics and Molecular Biology (ICYGMB)

August 27 – September 1, 2017
Prague, Czech Republic


Paper ID: 275

DNA End Resection and Repair Pathway Choice

Symington Lorraine, Oh Julyun, Yu Tai-Yuan

Columbia University (USA)

ABSTRACT

DNA double-strand breaks (DSBs) are cytotoxic lesions that must be accurately repaired to preserve genome integrity. DSBs can be repaired by direct ligation (NHEJ) or undergo 5’-3’ resection to generate single-stranded DNA (ssDNA), the substrate for homologous recombination (HR). Once resection initiates, cells are committed to HR. We have previously shown that resection of DNA ends occurs by a two-step mechanism (Mimitou and Symington, 2008). In the first step, the Mre11-Rad50-Xrs2 (MRX) complex and Sae2 incise the 5’ strands internal to the DNA ends to form an early intermediate. In a second step, Exo1 or Sgs1 with Dna2 rapidly process the minimally resected intermediates to generate long tracts of ssDNA. In addition to controlling end resection, the MRX complex is required for Tel1 signaling, NHEJ and for end tethering. Xrs2 is essential for nuclear translocation of Mre11, but its role as a component of the complex is not well defined. We found that fusion of a nuclear localization sequence to Mre11 (Mre11-NLS) was able to bypass several functions of Xrs2, including DNA end resection, hairpin resolution and cellular resistance to clastogens; however, NHEJ and Tel1 signaling were not restored indicating a unique function for Xrs2 in these processes (Oh et al, 2016). To further understand the role of Xrs2 in Tel1 signaling, we fused the Tel1 recruitment domain from Xrs2 to Mre11-NLS. The resulting fusion protein was able to bypass the role of Xrs2 in Tel1 recruitment and activation, restoring normal telomere length and Tel1 activation. We will discuss the roles of the MR complex, Xrs2 and Tel1 in DNA repair, HR and suppression of gross chromosome rearrangements. 

Keywords:
DNA repair, Homologous recombination, Mre11, Tel1
Presented as:
  Oral presentation [S8-1] in S8 DNA replication, mutation and repair

Institute of Microbiology

YEAST 2017
28th International Conference on Yeast Genetics and Molecular Biology (ICYGMB)

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