NEIL3 is a DNA glycosylase that removes oxidatively damaged bases from single-stranded DNA. Its expression is normally cell cycle regulated, peaking during S/G2 phase and is expressed only in highly proliferating cells, including paediatric cancer cell lines.
Recently, we have shown that NEIL3 and a related protein NEIL1 can excise DNA interstrand crosslinks (ICLs) in three- and four-stranded DNA structures that are thought to occur following stalled DNA replication fork bypass. To investigate this repair pathway further, cell lines deficient in Fanconi Anemia (FA) proteins, that are known to have a major role in ICL repair have been obtained. FA is a rare genetic disorder characterised by increased cancer predisposition, paticulary acute myeloid leukaemia, which is usually rare in children.
FA cells are hypersensitive to ICLs and to a lesser extent oxidative stress. Previous work has shown that overexpression of NEIL1 can complement FA hypersensitivity to cross-linking agents and furthermore, that the expression of NEIL1 is linked to an intact FA pathway, suggesting a association with the observed sensitivity to oxidative stress. The experiments proposed here will attempt to extend these findings to NEIL3.
Grant Award – Studentship 2018-2019
Funding Award – £2000
Funding Awarded to – Dr Rhod Elder
Research Location – University of Salford
Lead Researcher – Dr Rhod Elder
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