University of Calgary

Aditya Mojumdar

  • Postdoctoral Associate

Research Interest

Enhanced exposure to various harmful agents such as ultraviolet radiations, ionizing radiations, chemotherapeutic agents and/or oxidative stress leads to DNA damage. DNA double-strand breaks (DSBs) are one of the most toxic type of DNA damage, if left unrepaired, can lead to genomic instability and ultimately to cell death.

There are two main pathways that are evolutionary conserved from yeast to human for DSB repair: homologous recombination (HR) and non-homologous end joining (NHEJ). HR uses the sister chromatid as a template for the repair process and is active in late S and G2 stage of cell cycle, whereas NHEJ is active all along the cell cycle especially in G1 and G2 stages, uses a group of proteins that recognizes the break, binds and ligates it. NHEJ is an efficient and prompt way to repair DSBs, but also more error-prone than HR. NHEJ is the major DSB repair pathway in higher eukaryotes, particularly in mammals.

In mammalian(yeast homolog) NHEJ pathway, Ku70/80(YKu70/80) heterodimer recognizes and binds to broken DNA ends primarily protecting them from nucleolytic degradation. Subsequently the Ku heterodimer interacts with the catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) which is a serine/threonine kinase playing an essential role in tethering the broken DNA ends to a close proximity, remodeling the break site, and recruiting additional NHEJ factors. Once activated, the kinase phosphorylates the proteins involved in end-processing (APE1, FEN1, etc.) and ligation (XRCC4(Lif1)-DNA ligase IV(Dnl4) complex and XRCC4-like factor (XLF)(Nej1)).

The last step of ligation in NHEJ pathway is a very important step as a deficiency/mutation in any one of the components leads to severe immunodeficiency, embryonic lethality, genome instability, malignancy, bone marrow abnormalities and risk of cancer development. Hence a proper ligation of DSBs is a crucial step.

However, NHEJ needs to be suppressed at telomeres where the chromosome-internal DSBs co-exist because unwanted ligation can give rise to chromosome fusions and circular chromosomes. Hence a precise control of the ligation step of NHEJ is required. In order to achieve this control, several ligation factors carry post-translational modifications (PTM) such as phosphorylation and SUMOylation. In yeast, Nej1 (homologue of XLF) is phosphorylated as a DNA damage response by Dun1 DNA damage checkpoint kinase. Once phosphorylated, Nej1 interacts with Srs2 (a DNA helicase) and recruits it to DSB site, Srs2 dismantles inappropriately formed Rad51 nucleoprotein filaments hence promoting a proper NHEJ repair. Phosphorylation of another ligation factor in yeast Lif1 (homologue of XRCC4) enables an efficient recruitment of ligation factors to DSB sites.

I am interested in dissecting the role and regulation of these factors in DSB repair pathway choice.


Book Chapters/Contributions - Peer Reviewed

Journal Article

Journal Articles - Peer Reviewed

Technical Papers / Research Reports

Photograph of Aditya Mojumdar


  • PhD - Molecular Biomedicine
    University of Trieste, 2015
  • MS - Applied Biotechnology
    Uppsala University, 2010
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