Logo for University of Iowa Health Care This logo represents the University of Iowa Health Care

Lynne Dieckman

Mentor: Todd Washington, Ph.D.
Lab Room: 4-734 BSB
Lab Phone: 319-335-7501

Interactions between translesion synthesis DNA polymerase eta and ubiquitin-modified PCNA.

Classical DNA polymerases are unable to synthesize efficiently through DNA damaged templates, and thus normal replication is blocked at sites of DNA lesions. Non-classical polymerases, such as polymerase eta, exist to facilitate the bypass of the DNA damage so that our cells may overcome this stall in replication in order to divide. DNA polymerases utilize interactions with the sliding clamp PCNA (proliferating cell nuclear antigen) for recruitment to replication forks. PCNA is mono-ubiquitinated upon exposure to DNA damaging agents, and this is required for the replication past the damage by polymerase eta. Two mutant PCNA proteins (G178S and E113G) have been identified that support normal DNA replication and repair but are unable to support translesion synthesis in vivo. Our lab is interested in elucidating the interactions that take place during lesion bypass, the role of PCNA ubiquitination, and the role of the G178S mutation in the recruitment of non-classical polymerases during the replication of DNA damage. This knowledge is important because the replication of DNA damage has been shown to be the source of mutations, which play a fundamental part in carcinogenesis. Understanding how the recruitment of pol eta occurs, as well as how the G178S mutation in Ub-PCNA blocks translesion synthesis, may help in the development of strategies to regulate these events, perhaps by developing small molecule inhibitors that could prevent mutagenesis and consequently carcinogenesis.


Dieckman LM, Freudenthal BD, Washington MT. PCNA Structure and Function: Insights from Structures of PCNA Complexes and Post-translationally Modified PCNA. Subcell Biochem. 2012;62:281-99. PubMed PMID: 22918591.

Dieckman LM, Johnson RE, Prakash S, Washington MT. Pre-steady state kinetic studies of the fidelity of nucleotide incorporation by yeast DNA polymerase delta. Biochemistry. 2010 Aug 31;49(34):7344-50. PubMed PMID: 20666462; PubMed Central PMCID: PMC2941984.