Replication protein A (RPA) is a DNA single-strand binding protein essential for DNA replication, recombination and repair. In human cells treated with the topoisomerase inhibitors camptothecin or etoposide (VP-16), we find that RPA2, the middle-sized subunit of RPA, becomes rapidly phosphorylated. This response appears to be due to DNA-dependent protein kinase (DNA-PK) and to be independent of p53 or the ataxia telangiectasia mutated (ATM) protein. RPA2 phosphorylation in response to camptothecin required ongoing DNA replication. Camptothecin itself partially inhibited DNA synthesis, and this inhibition followed the same kinetics as DNA-PK activation and RPA2 phosphorylation. DNA-PK activation and RPA2 phosphorylation were prevented by the cell-cycle checkpoint abrogator 7-hydroxystaurosporine (UCN-01), which markedly potentiates camptothecin cytotoxicity. The DNA-PK catalytic subunit (DNA-PKcs) was found to bind RPA which was replaced by the Ku autoantigen upon camptothecin treatment. DNA-PKcs interacted directly with RPA1 in vitro. We propose that the encounter of a replication fork with a topoisomerase-DNA cleavage complex could lead to a juxtaposition of replication fork-associated RPA and DNA double-strand end-associated DNA-PK, leading to RPA2 phosphorylation which may signal the presence of DNA damage to an S-phase checkpoint mechanism.
Pharmacology, Toxicology and Pharmaceutical Science
2
1%
Chemistry
2
1%
Other
2
1%
Unknown
36
26%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 9. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 07 August 2021.
All research outputs
#5,140,275
of 34,357,314 outputs
Outputs from EMBO Journal
#3,553
of 14,095 outputs
Outputs of similar age
#6,552
of 52,838 outputs
Outputs of similar age from EMBO Journal
#28
of 136 outputs
Altmetric has tracked 34,357,314 research outputs across all sources so far. Compared to these this one has done well and is in the 83rd percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 14,095 research outputs from this source. They typically receive more attention than average, with a mean Attention Score of 9.6. This one has gotten more attention than average, scoring higher than 64% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 52,838 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 79% of its contemporaries.
We're also able to compare this research output to 136 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 63% of its contemporaries.
