Distinct roles of XPF-ERCC1 and Rad1-Rad10-Saw1 in replication-coupled and uncoupled inter-strand crosslink repair

Ja Hwan Seol, Cory Holland, Xiaolei Li, Christopher Kim, Fuyang Li, Melisa Medina-Rivera, Robin Eichmiller, Ignacio F. Gallardo, Ilya J. Finkelstein, Paul Hasty, Eun Yong Shim, Jennifer A. Surtees, Sang Eun Lee

Research output: Contribution to journalArticle

1 Scopus citations

Abstract

Yeast Rad1-Rad10 (XPF-ERCC1 in mammals) incises UV, oxidation, and cross-linking agent-induced DNA lesions, and contributes to multiple DNA repair pathways. To determine how Rad1-Rad10 catalyzes inter-strand crosslink repair (ICLR), we examined sensitivity to ICLs from yeast deleted for SAW1 and SLX4, which encode proteins that interact physically with Rad1-Rad10 and bind stalled replication forks. Saw1, Slx1, and Slx4 are critical for replication-coupled ICLR in mus81 deficient cells. Two rad1 mutations that disrupt interactions between Rpa1 and Rad1-Rad10 selectively disable non-nucleotide excision repair (NER) function, but retain UV lesion repair. Mutations in the analogous region of XPF also compromised XPF interactions with Rpa1 and Slx4, and are proficient in NER but deficient in ICLR and direct repeat recombination. We propose that Rad1-Rad10 makes distinct contributions to ICLR depending on cell cycle phase: in G1, Rad1-Rad10 removes ICL via NER, whereas in S/G2, Rad1-Rad10 facilitates NER-independent replication-coupled ICLR.

Original languageEnglish (US)
Article number4327
JournalNature communications
Volume9
Issue number1
DOIs
StatePublished - Dec 1 2018

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Seol, J. H., Holland, C., Li, X., Kim, C., Li, F., Medina-Rivera, M., Eichmiller, R., Gallardo, I. F., Finkelstein, I. J., Hasty, P., Shim, E. Y., Surtees, J. A., & Lee, S. E. (2018). Distinct roles of XPF-ERCC1 and Rad1-Rad10-Saw1 in replication-coupled and uncoupled inter-strand crosslink repair. Nature communications, 9(1), [4327]. https://doi.org/10.1038/s41467-018-04327-0