"RPA facilitates rescue of keratinocytes from UVB radiation damage thro" by Melisa J. Andrade, Derek R. Van Lonkhuyzen et al.
 

RPA facilitates rescue of keratinocytes from UVB radiation damage through insulin-like growth factor-I signalling

Document Type

Article

Publication Title

Journal of Cell Science

Abstract

UVBR-induced photolesions in genomic DNA of keratinocytes impair cellular functions and potentially determine the cell fate post-irradiation. The ability of insulin-like growth factor-I (IGF-I) to rescue epidermal keratinocytes after photodamage via apoptosis prevention and photolesion removal was recently demonstrated using in vitro twodimensional and three-dimensional skin models. Given the limited knowledge of specific signalling cascades contributing to post-UVBR IGF-I effects,we used inhibitors to investigate the impact of blockade of various signalling mediators on IGF-I photoprotection. IGF-I treatment, in the presence of signalling inhibitors, particularly TDRL-505, which targets replication protein A (RPA), impaired activation of IGF-1R downstream signalling, diminished cyclobutane pyrimidine dimer removal, arrested growth, reduced cell survival and increased apoptosis. Further, the transient partial knockdown of RPA was found to abrogate IGF-I-mediated responses in keratinocytes, ultimately affecting photoprotection and, thereby, establishing that RPA is required for IGF-I function. Our findings thus elucidate the importance of RPA in linking the damage response activation, cell cycle regulation, repair and survival pathways, separately initiated by IGF-I upon UVBRinduced damage. This information is potentially imperative for the development of effective sunburn and photodamage repair strategies.

DOI

10.1242/jcs.255786

Publication Date

6-1-2021

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