Excited to see my PhD work published @NAR_Open, describing an HR-independent #PARPi sensitivity upon loss of #polymerase epsilon accessory subunits POLE3-POLE4.
POLE4 loss enhances sensitivity of #BRCA1-deficiency & bypasses resistance due to 53BP1 loss.
https://t.co/9ut4jHT5B0
@Ella_Maru @NAR_Open Thank you @Ella! While we haven't tested it directly yet, we think it's due to POLE4 ensuring stable binding of polymerase complex to DNA. Upon its absence, continuous repriming leaves gaps accumulating behind the fork, exacerbating replication stress in BRCA1-deficient cells.
Immensely grateful to my supervisor Gyula Timinszky & Roberta Fajka-Boja (shared 1st author) for unforgettable journey.
It was a pleasure collaborating with Haracska lab (@BiologicalRese1) @SprteVillejean1, @bexsmithnz2, @sihemzenbio, @bowchro & Lakin lab (@BiochemOxford)
#PARPi leads to accumulation of ssDNA gaps in POLE4 KO, due to impaired post-replicative repair. This induces #replicationstress phenotypes mediated by ATR and DNA-PK.
Consequently, POLE4 KO are hypersensitive to ATRi and its combination with PARPi.
How to make cancer cells more sensitive to treatment. ๐
Preprint from @HasanMamar & team shows that the loss of POLE4 - component of POLฮต - contributes to PARPi sensitivity, regardless of BRCA status.
First preLight from @ANoireterre, check it out! ๐
https://t.co/8wnZDAqYzq
Thrilled to see my first first-author PrePrint online ๐, describing an HR independent sensitivity to PARPi upon deletion of accessory subunits of DNA pol epsilon.
Grateful to work with Roberta Fajka-Boja(co-first) and my supervisor Gyula Timinszky
#PARP#ADPribosylation
The loss of DNA polymerase epsilon accessory subunits POLE3-POLE4 leads to BRCA1-independent PARP inhibitor sensitivity https://t.co/Bzjo75qSRO #biorxiv_cellbio