RTEL1 suppresses G-quadruplex-associated R-loops at difficult-to-replicate loci in the human genome Journal Article
| Authors: | Wu, W.; Bhowmick, R.; Vogel, I.; Özer, Ö; Ghisays, F.; Thakur, R. S.; Sanchez de Leon, E.; Richter, P. H.; Ren, L.; Petrini, J. H.; Hickson, I. D.; Liu, Y. |
| Article Title: | RTEL1 suppresses G-quadruplex-associated R-loops at difficult-to-replicate loci in the human genome |
| Abstract: | Oncogene activation during tumorigenesis generates DNA replication stress, a known driver of genome rearrangements. In response to replication stress, certain loci, such as common fragile sites and telomeres, remain under-replicated during interphase and subsequently complete locus duplication in mitosis in a process known as ‘MiDAS’. Here, we demonstrate that RTEL1 (regulator of telomere elongation helicase 1) has a genome-wide role in MiDAS at loci prone to form G-quadruplex-associated R-loops, in a process that is dependent on its helicase function. We reveal that SLX4 is required for the timely recruitment of RTEL1 to the affected loci, which in turn facilitates recruitment of other proteins required for MiDAS, including RAD52 and POLD3. Our findings demonstrate that RTEL1 is required for MiDAS and suggest that RTEL1 maintains genome stability by resolving conflicts that can arise between the replication and transcription machineries. © 2020, The Author(s), under exclusive licence to Springer Nature America, Inc. |
| Keywords: | controlled study; unclassified drug; human cell; dna synthesis; mitosis; protein depletion; protein; gene locus; genomic instability; human genome; guanine quadruplex; gene replication; rad52 protein; scaffold protein; human; female; priority journal; article; slx4 protein; pold3 protein; r-loop structure; regulator of telomere elongation helicase 1 |
| Journal Title: | Nature Structural and Molecular Biology |
| Volume: | 27 |
| Issue: | 5 |
| ISSN: | 1545-9993 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2020-05-01 |
| Start Page: | 424 |
| End Page: | 437 |
| Language: | English |
| DOI: | 10.1038/s41594-020-0408-6 |
| PUBMED: | 32398827 |
| PROVIDER: | scopus |
| DOI/URL: | |
| Notes: | Article -- Export Date: 1 June 2020 -- Source: Scopus |
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