Poster
27

Resolution of R-loops by INO80 promotes DNA replication and maintains cancer cell proliferation and viability.

Authors

M Papamichos1
1 Universtiy of Liverpool, UK

Abstract

Collisions between the DNA replication machinery and co-transcriptional R-loops can impede DNA synthesis and are a major source of genomic instability in cancer cells. How cancer cells deal with R-loops to proliferate is poorly understood. Here we show that the ATP-dependent chromatin remodelling INO80 complex promotes resolution of R-loops to prevent replication-associated DNA damage in cancer cells. Depletion of INO80 in prostate cancer PC3 cells leads to increased R-loops. Overexpression of the RNA:DNA endonuclease RNAse H1 rescues the DNA synthesis defects and suppresses DNA damage caused by INO80 depletion. R-loops co-localize with and promote recruitment of INO80 to chromatin. Artificial tethering of INO80 to a LacO locus enabled turnover of R-loops in cis. Finally, counteracting R-loops by INO80 promotes proliferation and averts DNA damage-induced death in cancer cells. Our work suggests that INO80-dependent resolution of R-loops promotes DNA replication in the presence of transcription, thus enabling unlimited proliferation in cancers.

Reference:
Prendergast L, McClurg UL, Hristova R, Berlinguer-Palmini R, Greener S, Veitch K, Hernandez I, Pasero P, Rico D, Higgins JMG, Gospodinov A, and Papamichos-Chronakis M. (2020). Resolution of R-loops by INO80 promotes DNA replication and maintains cancer cell proliferation and viability. Nature Communications, 2020 Sep 10;11(1):4534.



Hosted By

ELRIG
The European Laboratory Research & Innovation Group Our Vision : To provide outstanding, leading edge knowledge to the life sciences community on an open access basis
Event Logo Find us on Facebook Follow us on Twitter

Get the App

Get this event information on your mobile by
going to the appstore or google play and search for 'elrig'
Eventflo Home
copyright ELRIG, eventflo.co.uk, Labhoo Ltd 2003-2021