Molecular, Cell, Development (MCD) Seminar Series - McMaster University
2008-09 || 2009-10 || 2010-11 || 2011-12 || 2012-13

Molecular, Cell, Development (MCD) SEMINAR SERIES
Department of Biology


 
Speaker: Megan McKerlie

Date: Friday 24th, May 2013
Time: 12 noon
Location: HSC 1A5

Title: TRF1 is recruited to sites of DNA damage to facilitate homologous recombination

Abstract
Telomeres are protein-DNA complexes found at the ends of linear eukaryotic chromosomes. These complexes serve to protect chromosome ends from being recognized as damaged DNA, which can lead to genomic instability. The precise regulation of telomere length and function is crucial to cell survival; defects in this coordination are related to tumorigenesis and premature aging disorders. TRF1, telomere repeat binding factor 1, is a protein that binds mammalian telomeric DNA and regulates telomere length. Post-translational modifications, such as phosphorylation, have been shown to alter TRF1 function. We have shown that TRF1 is phosphorylated at T371, rendering it free of telomeres. This fraction of TRF1 is recruited to sites of DNA damage following ionizing radiation, and forms DNA damage-induced foci. This foci formation is dependent upon ATM, BRCA1, and the MRN complex, and is negatively regulated by 53bp1. Depleting TRF1, or mutating T371 so as to prevent phosphorylation, impairs RPA foci formation and reduces homologous recombination. This phosphorylation site is also important for the activation of the G2/M checkpoint and for cell survival following the induction of DNA damage by PARP inhibition, ionizing radiation, or camptothecin treatment. This study reveals a novel function of TRF1 in the DNA damage response, in facilitation the repair of damaged DNA by homologous recombination.