PolDIP2 interacts with human PrimPol and enhances its DNA polymerase activities

Guilliam, Thomas A, Bailey, Laura J, Brissett, Nigel C and Doherty, Aidan J (2016) PolDIP2 interacts with human PrimPol and enhances its DNA polymerase activities. Nucleic Acids Research, 44 (7). pp. 3317-3329. ISSN 0305-1048

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Abstract

Translesion synthesis (TLS) employs specialized DNA polymerases to bypass replication fork stalling lesions. PrimPol was recently identified as a TLS primase and polymerase involved in DNA damage tolerance. Here, we identify a novel PrimPol binding partner, PolDIP2, and describe how it regulates PrimPol's enzymatic activities. PolDIP2 stimulates the polymerase activity of PrimPol, enhancing both its capacity to bind DNA and the processivity of the catalytic domain. In addition, PolDIP2 stimulates both the efficiency and error-free bypass of 8-oxo-7,8-dihydrodeoxyguanosine (8-oxoG) lesions by PrimPol. We show that PolDIP2 binds to PrimPol's catalytic domain and identify potential binding sites. Finally, we demonstrate that depletion of PolDIP2 in human cells causes a decrease in replication fork rates, similar to that observed in PrimPol−/− cells. However, depletion of PolDIP2 in PrimPol−/− cells does not produce a further decrease in replication fork rates. Together, these findings establish that PolDIP2 can regulate the TLS polymerase and primer extension activities of PrimPol, further enhancing our understanding of the roles of PolDIP2 and PrimPol in eukaryotic DNA damage tolerance.

Item Type: Article
Schools and Departments: School of Life Sciences > Sussex Centre for Genome Damage and Stability
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Depositing User: Nikoleta Kiapidou
Date Deposited: 20 Apr 2016 10:08
Last Modified: 07 Mar 2017 02:47
URI: http://sro.sussex.ac.uk/id/eprint/60558

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Project NameSussex Project NumberFunderFunder Ref
Understanding the role of PrimPol in damage tolerance during genome replication in eukaryotic cellsG1621BBSRC-BIOTECHNOLOGY & BIOLOGICAL SCIENCES RESEARCH COUNCILBB/M008800/1