| First Author | Kotsantis P | Year | 2020 |
| Journal | Cell Rep | Volume | 33 |
| Issue | 12 | Pages | 108546 |
| PubMed ID | 33357438 | Mgi Jnum | J:323531 |
| Mgi Id | MGI:6716697 | Doi | 10.1016/j.celrep.2020.108546 |
| Citation | Kotsantis P, et al. (2020) RTEL1 Regulates G4/R-Loops to Avert Replication-Transcription Collisions. Cell Rep 33(12):108546 |
| abstractText | Regulator of telomere length 1 (RTEL1) is an essential helicase that maintains telomere integrity and facilitates DNA replication. The source of replication stress in Rtel1-deficient cells remains unclear. Here, we report that loss of RTEL1 confers extensive transcriptional changes independent of its roles at telomeres. The majority of affected genes in Rtel1(-/-) cells possess G-quadruplex (G4)-DNA-forming sequences in their promoters and are similarly altered at a transcriptional level in wild-type cells treated with the G4-DNA stabilizer TMPyP4 (5,10,15,20-Tetrakis-(N-methyl-4-pyridyl)porphine). Failure to resolve G4-DNAs formed in the displaced strand of RNA-DNA hybrids in Rtel1(-/-) cells is suggested by increased R-loops and elevated transcription-replication collisions (TRCs). Moreover, removal of R-loops by RNaseH1 overexpression suppresses TRCs and alleviates the global replication defects observed in Rtel1(-/-) and Rtel1(PIP_box) knockin cells and in wild-type cells treated with TMPyP4. We propose that RTEL1 unwinds G4-DNA/R-loops to avert TRCs, which is important to prevent global deregulation in both transcription and DNA replication. |
