Ddx19 links mRNA nuclear export with progression of transcription and replication and suppresses genomic instability upon DNA damage in proliferating cells

Dana Hodroj (1) , Kamar Serhal (1) , Domenico Maiorano (1)

1 IGH - Institut de génétique humaine

The DEAD-box Helicase 19 (Ddx19) gene codes for an RNA helicase involved in both mRNA (mRNA) export from the nucleus into the cytoplasm and in mRNA translation. In unperturbed cells, Ddx19 localizes in the cytoplasm and at the cytoplasmic face of the nuclear pore. Here we review recent findings related to an additional Ddx19 function in the nucleus in resolving RNA:DNA hybrids (R-loops) generated during collision between transcription and replication, and upon DNA damage. Activation of a DNA damage response pathway dependent upon the ATR kinase, a major regulator of replication fork progression, stimulates translocation of the Ddx19 protein from the cytoplasm into the nucleus. Only nuclear Ddx19 is competent to resolve R-loops, and down regulation of Ddx19 expression induces DNA double strand breaks only in proliferating cells. Overall these observations put forward Ddx19 as an important novel mediator of the crosstalk between transcription and replication.

Mots clés: DNA damage; R-loop; camptothecin; mRNA; nuclear pore; proliferation; replication stress

Domaines: Sciences du Vivant [q-bio]; Génétique

Dana Hodroj, Kamar Serhal, Domenico Maiorano. Ddx19 links mRNA nuclear export with progression of transcription and replication and suppresses genomic instability upon DNA damage in proliferating cells. Nucleus, 2017, pp.1 - 7. ⟨10.1080/19491034.2017.1348448⟩. ⟨hal-01595942⟩