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Translesion DNA Synthesis

  • Chikahide MasutaniEmail author
  • Fumio Hanaoka
Chapter

Abstract

Human DNA polymerase η (pol η) is the gene product that is altered in the variant form of xeroderma pigmentosum. Pol η has a structure that can accommodate the cyclobutane pyrimidine dimer, the most prominent ultraviolet-induced DNA lesion. Pol η catalyzes efficient and accurate translesion DNA synthesis (TLS) under the fine control of systems involving interactions with mono-ubiquitinated proliferating cell nuclear antigen. Pol η can also catalyze TLS past cisplatin lesions, which might contribute to the resistance of tumors to chemotherapy. Other Y-family polymerases, pol ι, pol κ, and REV1, and a B-family polymerase pol ζ can contribute to erroneous TLS past ultraviolet-induced lesions. However, these polymerases also contribute to the maintenance of genomic stability in the presence of their cognate DNA lesions. A-family polymerases, pol θ and pol ν, also have TLS abilities, and pol θ has an important role in an alternative end-joining repair pathway for DNA double-strand breaks, protecting against genomic instability. PrimPol is a protein with DNA polymerase and primase activities that is capable of initiating de novo DNA/RNA synthesis and that also has the capacity to bypass modifications that stall the replisome, by TLS or origin-independent re-priming. This chapter summarizes our current knowledge relating to DNA polymerases that are capable of catalyzing TLS.

Keywords

Xeroderma pigmentosum variant Translesion DNA synthesis DNA damage tolerance DNA polymerase eta 

Notes

Acknowledgments

This work was supported by Grants-in-Aid from the Ministry of Education, Culture, Sports, Science, and Technology of Japan and by Takeda Science Foundation.

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Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  1. 1.Department of Genome DynamicsResearch Institute of Environmental Medicine, Nagoya UniversityNagoyaJapan
  2. 2.Department of Life Science, Graduate School of ScienceGakushuin UniversityTokyoJapan
  3. 3.Life Science Center for Survival Dynamics, Tsukuba Advanced Research AllianceUniversity of TsukubaTsukuba-shiJapan

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