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

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.

Medienart:

E-Artikel

Erscheinungsjahr:

2018

Erschienen:

2018

Enthalten in:

Zur Gesamtaufnahme - volume:9

Enthalten in:

Nature communications - 9(2018), 1 vom: 23. Mai, Seite 2025

Sprache:

Englisch

Beteiligte Personen:

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

Links:

Volltext

Themen:

Cross-Linking Reagents
DNA Repair Enzymes
DNA-Binding Proteins
EC 3.1.-
EC 3.1.30.1
EC 6.5.1.-
Endonucleases
Journal Article
RAD1 protein, S cerevisiae
RAD10 protein, S cerevisiae
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Saccharomyces cerevisiae Proteins
Saw1 protein, S cerevisiae
Single-Strand Specific DNA and RNA Endonucleases
Xeroderma pigmentosum group F protein

Anmerkungen:

Date Completed 11.12.2018

Date Revised 02.11.2022

published: Electronic

Citation Status MEDLINE

doi:

10.1038/s41467-018-04327-0

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM284409839