R-Loop-Associated Genomic Instability and Implication of WRN and WRNIP1
Maintenance of genome stability is crucial for cell survival and relies on accurate DNA replication. However, replication fork progression is under constant attack from different exogenous and endogenous factors that can give rise to replication stress, a source of genomic instability and a notable...
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| Format: | Article |
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MDPI AG
2022-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/3/1547 |
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| author | Veronica Marabitti Pasquale Valenzisi Giorgia Lillo Eva Malacaria Valentina Palermo Pietro Pichierri Annapaola Franchitto |
| author_facet | Veronica Marabitti Pasquale Valenzisi Giorgia Lillo Eva Malacaria Valentina Palermo Pietro Pichierri Annapaola Franchitto |
| author_sort | Veronica Marabitti |
| collection | DOAJ |
| description | Maintenance of genome stability is crucial for cell survival and relies on accurate DNA replication. However, replication fork progression is under constant attack from different exogenous and endogenous factors that can give rise to replication stress, a source of genomic instability and a notable hallmark of pre-cancerous and cancerous cells. Notably, one of the major natural threats for DNA replication is transcription. Encounters or conflicts between replication and transcription are unavoidable, as they compete for the same DNA template, so that collisions occur quite frequently. The main harmful transcription-associated structures are R-loops. These are DNA structures consisting of a DNA–RNA hybrid and a displaced single-stranded DNA, which play important physiological roles. However, if their homeostasis is altered, they become a potent source of replication stress and genome instability giving rise to several human diseases, including cancer. To combat the deleterious consequences of pathological R-loop persistence, cells have evolved multiple mechanisms, and an ever growing number of replication fork protection factors have been implicated in preventing/removing these harmful structures; however, many others are perhaps still unknown. In this review, we report the current knowledge on how aberrant R-loops affect genome integrity and how they are handled, and we discuss our recent findings on the role played by two fork protection factors, the Werner syndrome protein (WRN) and the Werner helicase-interacting protein 1 (WRNIP1) in response to R-loop-induced genome instability. |
| first_indexed | 2024-03-09T23:46:34Z |
| format | Article |
| id | doaj.art-3cce765f2af74f9690d7512038949d48 |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T23:46:34Z |
| publishDate | 2022-01-01 |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-3cce765f2af74f9690d7512038949d482023-11-23T16:42:15ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-01-01233154710.3390/ijms23031547R-Loop-Associated Genomic Instability and Implication of WRN and WRNIP1Veronica Marabitti0Pasquale Valenzisi1Giorgia Lillo2Eva Malacaria3Valentina Palermo4Pietro Pichierri5Annapaola Franchitto6Department of Environment and Health, Section of Mechanisms Biomarkers and Models, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, ItalyDepartment of Environment and Health, Section of Mechanisms Biomarkers and Models, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, ItalyDepartment of Environment and Health, Section of Mechanisms Biomarkers and Models, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, ItalyDepartment of Environment and Health, Section of Mechanisms Biomarkers and Models, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, ItalyDepartment of Environment and Health, Section of Mechanisms Biomarkers and Models, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, ItalyDepartment of Environment and Health, Section of Mechanisms Biomarkers and Models, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, ItalyDepartment of Environment and Health, Section of Mechanisms Biomarkers and Models, Istituto Superiore di Sanità, Viale Regina Elena 299, 00161 Rome, ItalyMaintenance of genome stability is crucial for cell survival and relies on accurate DNA replication. However, replication fork progression is under constant attack from different exogenous and endogenous factors that can give rise to replication stress, a source of genomic instability and a notable hallmark of pre-cancerous and cancerous cells. Notably, one of the major natural threats for DNA replication is transcription. Encounters or conflicts between replication and transcription are unavoidable, as they compete for the same DNA template, so that collisions occur quite frequently. The main harmful transcription-associated structures are R-loops. These are DNA structures consisting of a DNA–RNA hybrid and a displaced single-stranded DNA, which play important physiological roles. However, if their homeostasis is altered, they become a potent source of replication stress and genome instability giving rise to several human diseases, including cancer. To combat the deleterious consequences of pathological R-loop persistence, cells have evolved multiple mechanisms, and an ever growing number of replication fork protection factors have been implicated in preventing/removing these harmful structures; however, many others are perhaps still unknown. In this review, we report the current knowledge on how aberrant R-loops affect genome integrity and how they are handled, and we discuss our recent findings on the role played by two fork protection factors, the Werner syndrome protein (WRN) and the Werner helicase-interacting protein 1 (WRNIP1) in response to R-loop-induced genome instability.https://www.mdpi.com/1422-0067/23/3/1547genomic instabilityreplication stressDNA repairRecQ helicasesR-loops |
| spellingShingle | Veronica Marabitti Pasquale Valenzisi Giorgia Lillo Eva Malacaria Valentina Palermo Pietro Pichierri Annapaola Franchitto R-Loop-Associated Genomic Instability and Implication of WRN and WRNIP1 International Journal of Molecular Sciences genomic instability replication stress DNA repair RecQ helicases R-loops |
| title | R-Loop-Associated Genomic Instability and Implication of WRN and WRNIP1 |
| title_full | R-Loop-Associated Genomic Instability and Implication of WRN and WRNIP1 |
| title_fullStr | R-Loop-Associated Genomic Instability and Implication of WRN and WRNIP1 |
| title_full_unstemmed | R-Loop-Associated Genomic Instability and Implication of WRN and WRNIP1 |
| title_short | R-Loop-Associated Genomic Instability and Implication of WRN and WRNIP1 |
| title_sort | r loop associated genomic instability and implication of wrn and wrnip1 |
| topic | genomic instability replication stress DNA repair RecQ helicases R-loops |
| url | https://www.mdpi.com/1422-0067/23/3/1547 |
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