Changes in the architecture and abundance of replication intermediates delineate the chronology of DNA damage tolerance pathways at UV-stalled replication forks in human cells - Archive ouverte HAL Accéder directement au contenu
Article Dans Une Revue Nucleic Acids Research Année : 2022

Changes in the architecture and abundance of replication intermediates delineate the chronology of DNA damage tolerance pathways at UV-stalled replication forks in human cells

Pauline Dupaigne
Sonia Baconnais
Eliana Moreira Tavares
  • Fonction : Auteur
  • PersonId : 1289509
  • IdRef : 231157088
Gerard Mazón
Emmanuelle Despras
Eric Le Cam
Patricia L Kannouche

Résumé

DNA lesions in S phase threaten genome stability. The DNA damage tolerance (DDT) pathways overcome these obstacles and allow completion of DNA synthesis by the use of specialised translesion (TLS) DNA polymerases or through recombination-related processes. However, how these mechanisms coordinate with each other and with bulk replication remains elusive. To address these issues, we monitored the variation of replication intermediate architecture in response to ultraviolet irradiation using transmission electron microscopy. We show that the TLS polymerase , able to accurately bypass the major UV lesion and mutated in the skin cancer-prone xeroderma pigmentosum variant (XPV) syndrome, acts at the replication fork to resolve uncoupling and prevent post-replicative gap accumulation. Repriming occurs as a compensatory mechanism when this on-the-fly mechanism cannot operate, and is therefore predominant in XPV cells. Interestingly, our data support a recombination-independent function of RAD51 at the replication fork to sustain repriming. Finally, we provide evidence for the post-replicative commitment of recombination in gap repair and for pioneering observations of in vivo recombination intermediates. Altogether, we propose a chronology of UV damage tolerance in human cells that highlights the key role of pol in shaping this response and ensuring the continuity of DNA synthesis.
Fichier principal
Vignette du fichier
Benureau et al_gkac746.pdf (14.66 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte
Licence : CC BY NC - Paternité - Pas d'utilisation commerciale

Dates et versions

hal-03853540 , version 1 (15-11-2022)

Licence

Paternité - Pas d'utilisation commerciale

Identifiants

Citer

Yann Benureau, Caroline Pouvelle, Pauline Dupaigne, Sonia Baconnais, Eliana Moreira Tavares, et al.. Changes in the architecture and abundance of replication intermediates delineate the chronology of DNA damage tolerance pathways at UV-stalled replication forks in human cells. Nucleic Acids Research, 2022, 50 (17), pp.9909-9929. ⟨10.1093/nar/gkac746⟩. ⟨hal-03853540⟩
42 Consultations
44 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More