Enni MarkkanenDepartment of Veterinary Biochemistry and Molecular Biology, University of Zurich, Zurich, Switzerland F1000 Associate Faculty Member (since 04 May 2010)
Enni Markkanen is an Associate Faculty Member who works with Faculty Member Ulrich Hubscher to recommend the scientific literature in their field.Enni Markkanen also has responsibility for checking the contents of the following journals to ensure that the highest quality research relevant to their own interests within these publications is comprehensively and systematically evaluated for F1000:
PhD Student, Life Science Zurich Graduate School
Involvement and Regulation of DNA polymerase lambda in repair of oxidative DNA damage
Oxidative stress, stemming from endogenous or exogenous sources, causes damage to the highly reactive DNA bases via reactive oxygen species (ROS). Due to its prevalence and mutagenic potential 7,8-dihydro-8-oxo-2' deoxyguanine (8-oxo-G) is recognized as one of the most important oxidative DNA lesions. Most DNA polymerases show error-prone bypass of 8-oxo-G lesions, since they preferentially incorporate an Adenine opposite an 8-oxo-G instead of the correct Cytosine. This leads to GC -> TA transversion mutations that can eventually lead to cancer.
Our group has shown that the functional interaction of pol lambda with auxiliary factors PCNA and RP-A ensures that Cytosine is incorporated opposite a template 8-oxo-G 1200-fold more efficiently than Adenine. This and other recent findings by our lab suggest the existence of a 8-oxo-G repair pathway coordinated by MutYH glycosylase and pol lambda.
So far, only very little is known how the activity of those repair components is regulated in the cell. Posttranslational modifications, such as phosphorylation and ubiquitylation, provide a possibility of regulation of those proteins. It has been found that they orchestrate the stabilization, chromatin-recruitment and destruction of certain repair proteins. As chromatin-recruitment is a prerequisite for pol lambda to act, it would be very interesting to shed some light on this aspect.
The first part of the project addresses the question whether the in vitro data from our laboratory suggesting an involvement of pol lambda in error-free 8-oxo-G translesion synthesis hold true in vivo. In the second part of the project, the focus lies on the intricate network that coordinates stability, chromatin recruitment and proteasomal degradation of pol lambda.
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