For instance, RAD18 contributes to 5-fluorouracil (5-FU) resistance in colorectal cancer ( 22) and radiotherapy resistance in glioma ( 23). In addition to the vital roles in accurate cell replication and maintenance of genomic stability and integrity, accumulating evidence indicates that the DDR is also involved in resistance to DNA damage-based chemo- and radiotherapy. Importantly, these studies showed that RAD18 plays critical roles in sustaining retention of DNA polymerase at stalled replication forks and retention of 53BP1 and RAD51C at DNA lesions ( 13, 19–21). Furthermore, several reports have shown that RAD18 also contributes to DNA double-strand break repair either through the 53BP1-directed NHEJ pathway ( 19) or through the recombinase RAD51 paralog RAD51C-mediated HRR pathway ( 13). It has been reported that RAD18 formed a complex with RAD6, and subsequently promoted monoubiquitylation of proliferating cell nuclear antigen (PCNA) at stalled replication forks to recruit DNA polymerase, consequently leading to translesion DNA synthesis (TLS)-mediated post-replication repair (PRR) of damaged DNA ( 17, 18). Recent studies have demonstrated that RAD18 exerts its DNA repair function through multiple mechanisms ( 13–16). Therefore, stabilisation or retention of sensors, transducers and effectors at DNA lesions contributes to DNA damage repair. For instance, following DNA damage, the rapidly phosphorylated histone H2AX, referred to as γ-H2AX, which is a prerequisite for the sustained retention of signalling and repair proteins, recruits ring-type ubiquitin ligase RNF8 and, together with E2 ubiquitin conjugase 13 (UBC13), promotes protein ubiquitination at DNA damage sites, which facilitates the assembly of the RAD18 complex that transmits DNA damage signals ( 10–13). The DDR pathway consists of sensors, transducers and effectors that sense DNA damage, propagate the signal, and initiate the appropriate responses, such as cell cycle arrest, DNA repair or apoptosis ( 7–9). To prevent damaged genomic DNA-induced genetic instability ( 1–3), diverse DNA damage response (DDR) mechanisms, such as canonical homologous recombination repair (HRR) and non-homologous end-joining (NHEJ) pathways and the post-replication repair (PRR) pathway, have evolved to counteract different types of DNA damage ( 4–6). Genomic DNA in living organisms is highly vulnerable to exogenous and endogenous damage. Taken together, our results uncover a plausible mechanism underlying the DDR sustaining and might represent an attractive therapeutic strategy in improvement of DNA damage-based anticancer therapies. Importantly, treatment with ATR inhibitor abolished the effect of DDUP on chromatin retention of RAD51C and PCNA, thereby leading to hypersensitivity of cancer cells to DNA-damaging chemotherapeutics. Activated ATR kinase-mediated phosphorylation of DDUP induced a drastic ‘dense-to-loose’ conformational change, which sustained the RAD18/RAD51C and RAD18/PCNA complex at damaged sites and initiated RAD51C-mediated homologous recombination and PCNA-mediated post-replication repair mechanisms. Herein, we found that DNA damage provoked the association of ribosomes with IRES region in lncRNA CTBP1-DT, which overcame the negative effect of upstream open reading frames (uORFs), and elicited the novel microprotein DNA damage-upregulated protein (DDUP) translation via a cap-independent translation mechanism. She Moves Through The Fairīoyzone.Sustaining DNA damage response (DDR) signalling via retention of DDR factors at damaged sites is important for transmitting damage-sensing and repair signals. Secret Garden composed and sang this one. Daddy’s Little GirlĪl Martino crooned this waltzy number. Pink Floyd, gosh! You can never be comfortably numb, listening to their songs, can you! Stars Over Texas Kelly Clarkson, another popular young singer, enthralled many a listeners with this song. This song is the outcome of a joint venture of sorts by Bryan Adams, Rod Stewart and Sting! Wow! In the Still of the Nightīoys II Men, another popular band came up with this number. Could I Have This Dance For The Rest Of My Life