The identification of novel methylated proteins in DNA damage response
Year: 2010
Type: dissertation
Abstract: Protein methylation is a post-translational modification which can take place on both lysine and arginine residues. Classically, the characterization of these modifications on histones has shaped the field of epigenetics. These modifications are regulated by enzymes which specifically catalyze the transfer of a methyl group from a methyl donor to the amino groups of lysine or arginine residues. Methylation of non-histone proteins has also been proven to be crucial in many cellular processes. Understanding the role that protein methylation plays in DNA damage has elucidated the function of many proteins involved in the complex signalling cascade occurring at double-stranded DNA breaks (DSBs). Examining protein methylation has allowed us to identify new proteins implicated in DNA damage and to better clarify the function of existing proteins involved in the DNA damage response. The work presented in this thesis aims to develop new ways to identify methylated proteins involved in DNA damage as well as to verify any functional relevance of newly discovered proteins. Tudor domains traditionally have been shown to bind methylated residues. P53-binding protein 1 (53BP1) is a prominent mediator of DNA damage response and is recruited to DSBs via its tandem Tudor domain by binding methylated lysine on H4 histone protein. A proteomic screen of 53BP1's Tudor domain showed that it could bind brahma-related gene 1 (BRG1), a critical part of the human chromatin remodelling complex. One of the goals of the work presented in this thesis was to verify any in vivo significance of this interaction and if the chromatin remodelling complex plays a significant role in DNA damage response. The existence of an endogenous interaction was verified by a co-immunoprecipitation of BRG1 with 53BP1. In vivo methylation assay showed that BRG1 does in fact contain methylated residues. I hypothesised that 53BP1 could recruit BRG1 to DNA damage sites via this interaction, however, extensive analy
DOI: 10.82308/40431
Author: Salim, Ali
Language: English
Topic: DNA Repair Mechanisms
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W2187115734