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Int. J. Mol. Sci. 2011, 12(12), 8513-8529; doi:10.3390/ijms12128513
Article

Caffeine Abolishes the Ultraviolet-Induced REV3 Translesion Replication Pathway in Mouse Cells

1
, 1,†, 2 and 1,*
Received: 16 September 2011; in revised form: 8 November 2011 / Accepted: 17 November 2011 / Published: 29 November 2011
(This article belongs to the Special Issue UV-Induced Cell Death)
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Abstract: When a replicative DNA polymerase stalls upon encountering a photoproduct on the template strand, it is relieved by other low-processivity polymerase(s), which insert nucleotide(s) opposite the lesion. Using an alkaline sucrose density gradient sedimentation technique, we previously classified this process termed UV-induced translesion replication (UV-TLS) into two types. In human cancer cells or xeroderma pigmentosum variant (XP-V) cells, UV-TLS was inhibited by caffeine or proteasome inhibitors. However, in normal human cells, the process was insensitive to these reagents. Reportedly, in yeast or mammalian cells, REV3 protein (a catalytic subunit of DNA polymerase ζ) is predominantly involved in the former type of TLS. Here, we studied UV-TLS in fibroblasts derived from the Rev3-knockout mouse embryo (Rev3KO-MEF). In the wild-type MEF, UV-TLS was slow (similar to that of human cancer cells or XP-V cells), and was abolished by caffeine or MG-262. In 2 cell lines of Rev3KO-MEF (Rev3−/− p53−/−), UV-TLS was not observed. In p53KO-MEF, which is a strict control for Rev3KO-MEF, the UV-TLS response was similar to that of the wild-type. Introduction of the Rev3 expression plasmid into Rev3KO-MEF restored the UV-TLS response in selected stable transformants. In some transformants, viability to UV was the same as that in the wild-type, and the death rate was increased by caffeine. Our findings indicate that REV3 is predominantly involved in UV-TLS in mouse cells, and that the REV3 translesion pathway is suppressed by caffeine or proteasome inhibitors.
Keywords: alkaline sucrose density gradient sedimentation; caffeine; DNA polymerase ζ; proteasome inhibitor; TLS; translesion replication; Rev3 knockout alkaline sucrose density gradient sedimentation; caffeine; DNA polymerase ζ; proteasome inhibitor; TLS; translesion replication; Rev3 knockout
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Takezawa, J.; Aiba, N.; Kajiwara, K.; Yamada, K. Caffeine Abolishes the Ultraviolet-Induced REV3 Translesion Replication Pathway in Mouse Cells. Int. J. Mol. Sci. 2011, 12, 8513-8529.

AMA Style

Takezawa J, Aiba N, Kajiwara K, Yamada K. Caffeine Abolishes the Ultraviolet-Induced REV3 Translesion Replication Pathway in Mouse Cells. International Journal of Molecular Sciences. 2011; 12(12):8513-8529.

Chicago/Turabian Style

Takezawa, Jun; Aiba, Naomi; Kajiwara, Kagemasa; Yamada, Kouichi. 2011. "Caffeine Abolishes the Ultraviolet-Induced REV3 Translesion Replication Pathway in Mouse Cells." Int. J. Mol. Sci. 12, no. 12: 8513-8529.


Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert