The role of RECQL4 gene in cancer predispositon

Summary This project will test RecQL4 mutations associated with Rothmund-Thomson syndrome in a set of assays so that we may determine how the mutations directly impair DNA replication and/or repair.

Project Details

Mutations in the RecQL4 gene have been linked with cancer predisposition and three rare genetic disorders: Rothmund-Thomson syndrome, Baller-Gerold syndrome and RAPADILINO syndrome. Each have distinct phenotypes but all 3 syndromes eventually develop cancer at a young age. The current hypothesis to explain this high cancer incidence is that the RecQL4 gene is critical for 2 major cellular processes: DNA replication and DNA repair. In many other inherited or spontaneous forms of cancer, defects in DNA replication or DNA repair lead to acceleration of cancer development.

Our lab studies the mechanisms of the RecQL4 protein using protein chemistry and cell-based approaches. This project will test RecQL4 mutations associated with Rothmund-Thomson syndrome in a set of assays so that we may determine how the mutations directly impair DNA replication and/or repair. The student will utilize a state-of-the-art protein expression system to produce the RecQL4 proteins, and test their biochemical function compared to wild-type protein. Mouse models of Rothmund-Thomson syndrome are also available to test the findings from the in vitro work, at the cellular and whole organism level.

This project is conducted in St Vincent’s Institute of Medical Research, Genome Stability Unit.