Journal
NUCLEIC ACIDS RESEARCH
Volume 41, Issue 3, Pages 1661-1668Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gks1267
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Funding
- American Cancer Society Research Scholar
- Minnesota Partnership for Biotechnology and Medical Genomics
- NIH [R01 GM089778, 5 U01AI082120-04]
- Jonsson Cancer Center at UCLA
- American Cancer Society
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Translesion synthesis (TLS) employs low fidelity polymerases to replicate past damaged DNA in a potentially error-prone process. Regulatory mechanisms that prevent TLS-associated mutagenesis are unknown; however, our recent studies suggest that the PCNA-binding protein Spartan plays a role in suppression of damage-induced mutagenesis. Here, we show that Spartan negatively regulates error-prone TLS that is dependent on POLD3, the accessory subunit of the replicative DNA polymerase Pol delta. We demonstrate that the putative zinc metalloprotease domain SprT in Spartan directly interacts with POLD3 and contributes to suppression of damage-induced mutagenesis. Depletion of Spartan induces complex formation of POLD3 with Rev1 and the error-prone TLS polymerase Pol zeta, and elevates mutagenesis that relies on POLD3, Rev1 and Pol zeta. These results suggest that Spartan negatively regulates POLD3 function in Rev1/Pol zeta-dependent TLS, revealing a previously unrecognized regulatory step in error-prone TLS.
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