Title of Oral/Poster Presentation

Role of SRS-2 Helicase in Homologous Recombination

Presenter Information

Elliot CorlessFollow

Class

Article

Department

Chemistry and Biochemistry

Faculty Mentor

Edwin Antony

Presentation Type

Poster Presentation

Abstract

Cancers arise primarily due to the accumulation of DNA damage resulting in instability of the genome. DNA damage in the sequence of a gene that codes for a protein results in dysfunctional proteins. Double stranded DNA (dsDNA) breaks are the most mutagenic types of DNA damage - often caused by cellular metabolic byproducts (reactive oxygen species), or exposure to ionizing radiation. Cells use two DNA repair methods to correct dsDNA breaks: Homologous Recombination (HR) and Non-Homologous End Joining (NHEJ). HR is more accurate during repair and is preferentially used over NHEJ. A protein called Rad51 is the engine for HR and works by binding to the broken DNA and uses the undamaged allele as a template to repair the break. Mediator proteins control the timing of HR by either promoting Rad51 binding (pro-HR mediators) or by removing Rad51 from the DNA (anti-HR mediators). The Srs2 helicase is an anti-homologous recombination mediator and my project focuses on its mechanism of action. Srs2 is made up of four conserved domains: 1A, 1B, 2A and 2B. The 2B domain in particular appears to possess regulatory functions. We hypothesize that the 2B domain in Srs2 promotes interaction between two Srs2 molecules and regulates its activity in HR. We have isolated the 2B domain and biochemically show that it forms a dimer in solution. My project explores how the 2B domain works on a structural, biochemical, and cellular level to shed light on the mechanism of Srs2 function. This knowledge would lead to a better understanding on the mechanism of HR and the emergence of cancers.

Start Date

4-9-2015 3:00 PM

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Apr 9th, 3:00 PM

Role of SRS-2 Helicase in Homologous Recombination

Cancers arise primarily due to the accumulation of DNA damage resulting in instability of the genome. DNA damage in the sequence of a gene that codes for a protein results in dysfunctional proteins. Double stranded DNA (dsDNA) breaks are the most mutagenic types of DNA damage - often caused by cellular metabolic byproducts (reactive oxygen species), or exposure to ionizing radiation. Cells use two DNA repair methods to correct dsDNA breaks: Homologous Recombination (HR) and Non-Homologous End Joining (NHEJ). HR is more accurate during repair and is preferentially used over NHEJ. A protein called Rad51 is the engine for HR and works by binding to the broken DNA and uses the undamaged allele as a template to repair the break. Mediator proteins control the timing of HR by either promoting Rad51 binding (pro-HR mediators) or by removing Rad51 from the DNA (anti-HR mediators). The Srs2 helicase is an anti-homologous recombination mediator and my project focuses on its mechanism of action. Srs2 is made up of four conserved domains: 1A, 1B, 2A and 2B. The 2B domain in particular appears to possess regulatory functions. We hypothesize that the 2B domain in Srs2 promotes interaction between two Srs2 molecules and regulates its activity in HR. We have isolated the 2B domain and biochemically show that it forms a dimer in solution. My project explores how the 2B domain works on a structural, biochemical, and cellular level to shed light on the mechanism of Srs2 function. This knowledge would lead to a better understanding on the mechanism of HR and the emergence of cancers.