Disruption of Protein–DNA Interactions: An Opportunity for Cancer Chemotherapy

Neher, Tracy M.; Huang, Wei; Zhang, Jian-Ting; Turchi, John J.

doi:10.5772/22387

Cited by 1 publication

(1 citation statement)

References 102 publications

(97 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…TDRL-505 targets RPA, which possesses roles in replication, recombination, stress responses and most importantly NER. Inhibition of RPA by TDRL-505 results in DNA damage accumulation after UVBR, which in turn leads to cell death (Neher et al, 2011). Hence, the decreased cell viability observed could be indicative of TDRL-505-induced cell death.…”

Section: Effect Of Inhibitors On the Igf-i-mediated Rescue Pathway In Irradiated Monolayer Primary Keratinocytesmentioning

confidence: 99%

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

Andrade

Lonkhuyzen

Upton

et al. 2021

Journal of Cell Science

View full text Add to dashboard Cite

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 2D and 3D 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 CPD 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, elucidated the importance of RPA in linking the damage response activation, cell cycle regulation, repair and survival pathways, separately initiated by IGF-I upon UVBR-induced damage, information that is potentially imperative for the development of effective sunburn and photodamage repair strategies.

show abstract

Section: Effect Of Inhibitors On the Igf-i-mediated Rescue Pathway In Irradiated Monolayer Primary Keratinocytesmentioning

confidence: 99%