TY - JOUR
T1 - Distinct roles of XPF-ERCC1 and Rad1-Rad10-Saw1 in replication-coupled and uncoupled inter-strand crosslink repair
AU - Seol, Ja Hwan
AU - Holland, Cory
AU - Li, Xiaolei
AU - Kim, Christopher
AU - Li, Fuyang
AU - Medina-Rivera, Melisa
AU - Eichmiller, Robin
AU - Gallardo, Ignacio F.
AU - Finkelstein, Ilya J.
AU - Hasty, Paul
AU - Shim, Eun Yong
AU - Surtees, Jennifer A.
AU - Lee, Sang Eun
N1 - Funding Information:
We thank J. Haber, R. Kolodner, R. Nairn, R. Rothstein, and X. Zhao for reagents and the plasmids for the study. We thank Dr. Mark Sutton for providing E. coli SSB and for helpful discussions. We are also grateful to the members of the Lee and Surtees labs for helpful discussions and to Dr. Eugen Minca for performing some initial experiments. This work was supported by William and Ella Owen Medical Research Foundation and NIH research grant GM71011 to S.E.L., ThriveWell Cancer Foundation to E.Y. S., ES022054 and CA188032 to P.H., GM097177 to I.J.F., IMSD R25 GM095459, and a diversity supplement to GM066094 to M.M.R. and GM87459 to J.A.S.
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
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UR - http://www.scopus.com/inward/citedby.url?scp=85047519637&partnerID=8YFLogxK
U2 - 10.1038/s41467-018-04327-0
DO - 10.1038/s41467-018-04327-0
M3 - Article
C2 - 29795289
AN - SCOPUS:85047519637
VL - 9
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
IS - 1
M1 - 2025
ER -