Journal
NUCLEIC ACIDS RESEARCH
Volume 36, Issue 21, Pages 6767-6780Publisher
OXFORD UNIV PRESS
DOI: 10.1093/nar/gkn651
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Funding
- Medical Research Council
- Leukaemia Research Fund [04046]
- MRC [MC_U105178808] Funding Source: UKRI
- Medical Research Council [MC_U105178808] Funding Source: researchfish
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Exposure to ultraviolet light induces a number of forms of damage in DNA, of which (64) photoproducts present the most formidable challenge to DNA replication. No single DNA polymerase has been shown to bypass these lesions efficiently in vitro suggesting that the coordinate use of a number of different enzymes is required in vivo. To further understand the mechanisms and control of lesion bypass in vivo, we have devised a plasmid-based system to study the replication of site-specific TT(64) photoproducts in chicken DT40 cells. We show that DNA polymerase is absolutely required for translesion synthesis (TLS) of this lesion, while loss of DNA polymerase has no detectable effect. We also show that either the polymerase-binding domain of REV1 or ubiquitinated PCNA is required for the recruitment of Pol as the catalytic TLS polymerase. Finally, we demonstrate a previously unappreciated role for REV1 in ensuring bypass synthesis remains in frame with the template. Our data therefore suggest that REV1 not only helps to coordinate the delivery of DNA polymerase to a stalled primer terminus but also restrains its activity to ensure that nucleotides are incorporated in register with the template strand.
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