PT  - JOURNAL ARTICLE
AU  - Menattallah Elserafy
AU  - Iman El-Shiekh
AU  - Dalia Fleifel
AU  - Reham Atteya
AU  - Abdelrahman AlOkda
AU  - Mohamed M Abdrabbou
AU  - Mostafa Nasr
AU  - Sherif F El-Khamisy
TI  - A role for Rad5 in ribonucleoside monophosphate (rNMP) tolerance
AID  - 10.26508/lsa.202000966
DP  - 2021 Oct 01
TA  - Life Science Alliance
PG  - e202000966
VI  - 4
IP  - 10
4099  - https://www.life-science-alliance.org/content/4/10/e202000966.short
4100  - https://www.life-science-alliance.org/content/4/10/e202000966.full
SO  - Life Sci. Alliance2021 Oct 01; 4
AB  - Ribonucleoside monophosphate (rNMP) incorporation in genomic DNA poses a significant threat to genomic integrity. In addition to repair, DNA damage tolerance mechanisms ensure replication progression upon encountering unrepaired lesions. One player in the tolerance mechanism is Rad5, which is an E3 ubiquitin ligase and helicase. Here, we report a new role for yeast Rad5 in tolerating rNMP incorporation, in the absence of the bona fide ribonucleotide excision repair pathway via RNase H2. This role of Rad5 is further highlighted after replication stress induced by hydroxyurea or by increasing rNMP genomic burden using a mutant DNA polymerase (Pol ε - Pol2-M644G). We further demonstrate the importance of the ATPase and ubiquitin ligase domains of Rad5 in rNMP tolerance. These findings suggest a similar role for the human Rad5 homologues helicase-like transcription factor (HLTF) and SNF2 Histone Linker PHD RING Helicase (SHPRH) in rNMP tolerance, which may impact the response of cancer cells to replication stress-inducing therapeutics.