Protein Phosphatase 2A–Dependent Mitotic hnRNPA1 Dephosphorylation and TERRA Formation Facilitate Telomere Capping

The heterogeneous nuclear ribonucleoprotein A1 (hnRNPA1), hnRNPA1-to-POT1 switch on telomeric single-stranded DNA. telomeric repeat-containing RNA (TERRA), and protection of Consequently, defective PPP2R1A results in ataxia telangiectasia telomeres 1 (POT1) have been reported to orchestrate to displace and Rad3-related (ATR)-mediated DNA damage response at tel-replication protein A (RPA) from telomeric overhangs, ensuring omeres as well as induction of fragile telomeres. Combined inhiorderly telomere replication and capping. Our previous studies bition of ATR and PP2A induces entry into a catastrophic mitosis further demonstrated that DNA-dependent protein kinase catalytic and leads to synthetic lethality of tumor cells. In addition, PPP2R1A subunit (DNA-PKcs)-dependent hnRNPA1 phosphorylation plays levels correlate with clinical stages and prognosis of multiple types a crucial role in the promotion of hnRNPA1 binding to telomeric of cancers. Taken together, our results indicate that PP2A is critical overhangs and RPA displacement during G₂–M phases. However, it for telomere maintenance. is unclear that how the subsequent exchange between hnRNPA1 and POT1 is orchestrated. Here we report that the protein phosImplications: This study demonstrates that the PP2A-dependent phatase 2A (PP2A) depends on its scaffold subunit, which is called hnRNPA1 dephosphorylation and TERRA accumulation facilPPP2R1A, to interact with and dephosphorylate hnRNPA1 in the itates the formation of the protective capping structure of newly late M phase. Furthermore, PP2A-mediated hnRNPA1 dephosreplicated telomeres, thus exerting essential oncogenic role in phorylation and TERRA accumulation act in concert to promote the tumorigenesis.