Telomere length dynamics in response to DNA damage in malaria parasites
Jake Reed,
Laura A. Kirkman,
Björn F. Kafsack,
Christopher E. Mason,
Kirk W. Deitsch
Affiliations
Jake Reed
Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY, USA
Laura A. Kirkman
Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY, USA; Department of Internal Medicine, Division of Infectious Diseases, Weill Cornell Medical College, New York, NY, USA
Björn F. Kafsack
Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY, USA
Christopher E. Mason
Department of Physiology and Biophysics, Weill Cornell Medical College, New York, NY, USA; Jill Roberts Center for Inflammatory Bowel Disease, Weill Cornell Medical College, New York, NY, USA; HRH Prince Alwaleed Bin Talal Bin Abdulaziz Alsaud Institute for Computational Biomedicine, Weill Cornell Medical College, New York, NY, USA; Feil Family Brain and Mind Research Institute, Weill Cornell Medical College, New York, NY, USA; WorldQuant Initiative for Quantitative Prediction, Weill Cornell Medical College, New York, NY, USA; Corresponding author
Kirk W. Deitsch
Department of Microbiology and Immunology, Weill Cornell Medical College, New York, NY, USA; Corresponding author
Summary: Malaria remains a major cause of morbidity and mortality in the developing world. Recent work has implicated chromosome end stability and the repair of DNA breaks through telomere healing as potent drivers of variant antigen diversification, thus associating basic mechanisms for maintaining genome integrity with aspects of host-parasite interactions. Here we applied long-read sequencing technology to precisely examine the dynamics of telomere addition and chromosome end stabilization in response to double-strand breaks within subtelomeric regions. We observed that the process of telomere healing induces the initial synthesis of telomere repeats well in excess of the minimal number required for end stability. However, once stabilized, these newly created telomeres appear to function normally, eventually returning to a length nearing that of intact chromosome ends. These results parallel recent observations in humans, suggesting an evolutionarily conserved mechanism for chromosome end repair.
