Anna Konopka

Title : Wildtype TDP-43 functions in DNA repair but this process is perturbed in amyotrophic lateral sclerosis (ALS)

Abstract:

Pathological forms of TAR DNA-binding protein 43 (TDP-43) are present in motor neurons of almost all amyotrophic lateral sclerosis (ALS) patients, and mutations in TDP-43 are present in familial ALS. Loss and gain of TDP-43 functions are implicated in pathogenesis but the mechanisms are unclear. Here we demonstrate that wildtype TDP-43 is recruited to sites of DNA damage where it participates in non-homologous end joining (NHEJ) DNA repair.  However, ALS-associated TDP-43 mutants lose this activity, which induces DNA damage.  Furthermore, DNA damage is present in mice displaying TDP-43 pathology prior to disease, implying an active role in neurodegeneration. Additionally, DNA damage triggers features of TDP-43 pathology; cytoplasmic mislocalisation and stress granule formation. This study reveals that TDP-43 functions in DNA damage/DNA repair, but loss of this function triggers DNA damage and associates with key pathological features of ALS.  

Biography:

Dr Anna Konopka obtained her PhD degree in 2015 from the Nencki Institute of Experimental Biology, Polish Academy of Science in Warsaw, Poland. Her research resulted in two first author papers and six co-authored papers. Since January 2017 Dr Konopka have been employed as a postdoctoral research fellow at Macquarie University, Sydney, Australia working within Prof Atkin’s group on DNA damage in neurodegeneration in ALS. Since joining Prof Atkin’s laboratory Dr Konopka have published four journal articles. Her publications reflect her research interests in neurodegeneration in ALS, particularly interests in DNA damage in neurodegeneration.