ATRX: characterisation of a novel player in DNA damage repair

ATRX has recently been identified as a key tumour suppressor in a variety of cancers. In many of these cancers, mutations in ATRX are associated with a telomerase independent telomere length maintenance pathway, denoted the ‘Alternative lengthening of telomeres’ (ALT) pathway which permits the tumour cells to divide indefinitely. This pathway is thought to be related to ATRX’s role in DNA replication (1, 2). However, accumulating evidence suggests that ATRX may also play a direct role in DNA repair, with loss of ATRX resulting in reduced recovery of cells from UV irradiation (3). Moreover, ATRX has been shown to localise to sites of DNA damage (4) and interacts with multiple key players in DNA damage repair (1 and unpublished). Despite this, very little is known about the mechanistic role ATRX plays at sites of DNA damage. The proposed project will aim to address this using a variety of systematic approaches, including live cell imaging techniques to assess the recruitment of factors to DNA damage sites in real time.

Training Opportunities
In addition to standard molecular/cellular biology techniques this studentship will provide training in a variety of cutting edge scientific methods including: ultra high resolution microscopy and imaging methods, genome editing (CRISPR-Cas9 based gene tagging and deletion). There is also an opportunity to learn biochemical/biophysical characterisations of protein-protein and protein-DNA interactions through our collaborators.