Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

REV1 Inhibition Enhances Radioresistance and Autophagy

Kanayo Ikeh
,
Erica Lamkin
ORCID logo ,
Andrew Crompton
ORCID logo ,
Jamie Deutsch
,
Kira Fisher
,
Mark E. Gray
,
David Argyle
,
Won Lim
,
Dmitry Korzhnev
,
M. Kyle Hadden
ORCID logo ,
Jiyong Hong
ORCID logo ,
Pei Zhou
ORCID logo ,
Nimrat Chatterjee
*
Version 1 : Received: 9 September 2021 / Approved: 13 September 2021 / Online: 13 September 2021 (11:09:07 CEST)

A peer-reviewed article of this Preprint also exists.

Ikeh, K.E.; Lamkin, E.N.; Crompton, A.; Deutsch, J.; Fisher, K.J.; Gray, M.; Argyle, D.J.; Lim, W.Y.; Korzhnev, D.M.; Hadden, M.K.; Hong, J.; Zhou, P.; Chatterjee, N. REV1 Inhibition Enhances Radioresistance and Autophagy. Cancers 2021, 13, 5290. Ikeh, K.E.; Lamkin, E.N.; Crompton, A.; Deutsch, J.; Fisher, K.J.; Gray, M.; Argyle, D.J.; Lim, W.Y.; Korzhnev, D.M.; Hadden, M.K.; Hong, J.; Zhou, P.; Chatterjee, N. REV1 Inhibition Enhances Radioresistance and Autophagy. Cancers 2021, 13, 5290.

Abstract

Cancer therapy resistance is a persistent clinical challenge. Recently, inhibition of the mutagenic translesion synthesis (TLS) protein REV1 was shown to enhance tumor cell response to chemotherapy by triggering senescence hallmarks. These observations suggest REV1’s important role in determining cancer cell response to chemotherapy. Whether REV1 inhibition would similarly sensitize cancer cells to radiation treatment is unknown. This study reports a lack of radiosensitization in response to REV1 inhibition by small molecule inhibitors in ionizing radiation-exposed cancer cells. Instead, REV1 inhibition unexpectedly triggers autophagy, which is a known biomarker of radioresistance. Collectively, we report a possible role of REV1 TLS protein in determining cancer treatment outcomes depending upon the type of DNA damage inflicted. Furthermore, we discover REV1 inhibition directly triggers autophagy, an uncharacterized REV1 phenotype, with significant bearing on cancer treatment regimens.

Keywords

Translesion synthesis; radioresistance; autophagy; REV1; ionizing radiations; etoposide

Subject

Biology and Life Sciences, Immunology and Microbiology

Copyright: 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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