Investigating how the replication protein DONSON maintains genome stability

Vernet, Audrey (2018). Investigating how the replication protein DONSON maintains genome stability. University of Birmingham. M.Sc.

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Abstract

DNA replication is a fundamental cellular process that ensures accurate and efficient duplication of genetic information before subsequent transmission to daughter cells. If left unresolved, DNA replication stress, referring to anything that obstructs, slows, or stalls replication forks, leads to increased genetic instability. Elevated DNA replication stress and defective DNA repair are common underlying causes of several human diseases. Recently, our laboratory has identified DONSON (Downstream Neighbour Of SON) as a human gene that is mutated in patients with microcephalic dwarfism. The DONSON protein is a replisome component that is essential for maintaining genome stability by regulating the ATR-dependent DNA damage response (DDR), stabilising replication forks and facilitating cell cycle checkpoint activation, although how post-translational modifications affect DONSON functions are as yet unknown. Using a combination of in vivo and in vitro assays, we demonstrate here that DONSON undergoes post-translational modifications (PTMs) within its N-terminus. We also identify enzymes that interact with and catalyse DONSON PTMs as well as specific sites modified within the N-terminal region. Further investigation will hopefully reveal how these modifications regulate the cellular functions of DONSON in the context of DNA replication and activation of the DDR.

Type of Work:

Thesis (Masters by Research > M.Sc.)

Award Type:

Masters by Research > M.Sc.

Supervisor(s):