Looping out of control: R-loops in transcription-replication conflict Review
| Authors: | Kumar, C.; Remus, D. |
| Review Title: | Looping out of control: R-loops in transcription-replication conflict |
| Abstract: | Transcription-replication conflict is a major cause of replication stress that arises when replication forks collide with the transcription machinery. Replication fork stalling at sites of transcription compromises chromosome replication fidelity and can induce DNA damage with potentially deleterious consequences for genome stability and organismal health. The block to DNA replication by the transcription machinery is complex and can involve stalled or elongating RNA polymerases, promoter-bound transcription factor complexes, or DNA topology constraints. In addition, studies over the past two decades have identified co-transcriptional R-loops as a major source for impairment of DNA replication forks at active genes. However, how R-loops impede DNA replication at the molecular level is incompletely understood. Current evidence suggests that RNA:DNA hybrids, DNA secondary structures, stalled RNA polymerases, and condensed chromatin states associated with R-loops contribute to the of fork progression. Moreover, since both R-loops and replication forks are intrinsically asymmetric structures, the outcome of R-loop-replisome collisions is influenced by collision orientation. Collectively, the data suggest that the impact of R-loops on DNA replication is highly dependent on their specific structural composition. Here, we will summarize our current understanding of the molecular basis for R-loop-induced replication fork progression defects. © The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2023. |
| Keywords: | genetics; dna replication; chromosome; chemistry; dna; genomic instability; transcription; chromosomes; dna directed rna polymerase; dna-directed rna polymerases; genome stability; rna polymerase; r-loops; humans; human; r-loop structure; r-loop structures |
| Journal Title: | Chromosoma |
| Volume: | 133 |
| Issue: | 1 |
| ISSN: | 0009-5915 |
| Publisher: | Springer |
| Date Published: | 2024-01-01 |
| Start Page: | 37 |
| End Page: | 56 |
| Language: | English |
| DOI: | 10.1007/s00412-023-00804-8 |
| PUBMED: | 37419963 |
| PROVIDER: | scopus |
| PMCID: | PMC10771546 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding author is MSK author: Dirk Remus -- Source: Scopus |
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