Description
This track integrates RPA1, RPA2 and pRPA2 ChIP-seq datasets. The RPA complex (RPA1/RPA2/RPA3) has high affinity for ssDNA and is recruited to the displaced strand of R-loops, therefore providing a complementary readout to direct RNA:DNA hybrid mapping. In contrast, pRPA2 (the ATR-phosphorylated form of RPA2 at serine 33) specifically reports the activation of the replication stress response. Phosphorylation of RPA2 by ATR occurs when R-loops physically interfere with replication fork progression, primarily at transcription termination sites (TTS) that are replicated in a head-on orientation relative to transcription. Thus, while RPA1/RPA2 indicate the presence of R-loop-associated ssDNA, pRPA2 distinguishes which R-loop regions cause replication fork stalling and ATR activation.
Reference
Zhang H, Gan H, Wang Z, RPA interacts with HIRA and regulates H3.3 deposition at gene regulatory elements in mammalian cells. Mol Cell. 2017 Jan 19;65(2):272-284. PMID: 28107649
Promonet A, Padioleau I, Liu Y et al, Topoisomerase 1 prevents replication stress at R-loop-enriched transcription termination sites. Nat Commun. 2020 Aug 7;11(1):3940. PMID: 32769985
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