SLX4IP Acts with SLX4 and XPF-ERCC1 to Promote Interstrand Crosslink Repair

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2019 Sep 10

PMID 31495888

Citations 21

Authors

Huimin Zhang

Zhen Chen

Yin Ye

Zu Ye

Dan Cao

Yun Xiong

Mrinal Srivastava

Xu Feng

Mengfan Tang

Chao Wang

John A Tainer

Junjie Chen

Affiliations

Soon will be listed here.

Abstract

Interstrand crosslinks (ICLs) are highly toxic DNA lesions that are repaired via a complex process requiring the coordination of several DNA repair pathways. Defects in ICL repair result in Fanconi anemia, which is characterized by bone marrow failure, developmental abnormalities, and a high incidence of malignancies. SLX4, also known as FANCP, acts as a scaffold protein and coordinates multiple endonucleases that unhook ICLs, resolve homologous recombination intermediates, and perhaps remove unhooked ICLs. In this study, we explored the role of SLX4IP, a constitutive factor in the SLX4 complex, in ICL repair. We found that SLX4IP is a novel regulatory factor; its depletion sensitized cells to treatment with ICL-inducing agents and led to accumulation of cells in the G2/M phase. We further discovered that SLX4IP binds to SLX4 and XPF-ERCC1 simultaneously and that disruption of one interaction also disrupts the other. The binding of SLX4IP to both SLX4 and XPF-ERCC1 not only is vital for maintaining the stability of SLX4IP protein, but also promotes the interaction between SLX4 and XPF-ERCC1, especially after DNA damage. Collectively, these results demonstrate a new regulatory role for SLX4IP in maintaining an efficient SLX4-XPF-ERCC1 complex in ICL repair.

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References

Genuardi M, Chiurazzi P, Capelli A, Neri G . X-linked VACTERL with hydrocephalus: the VACTERL-H syndrome. Birth Defects Orig Artic Ser. 1993; 29(1):235-41. View

Hodskinson M, Silhan J, Crossan G, Garaycoechea J, Mukherjee S, Johnson C . Mouse SLX4 is a tumor suppressor that stimulates the activity of the nuclease XPF-ERCC1 in DNA crosslink repair. Mol Cell. 2014; 54(3):472-84. PMC: 4017094. DOI: 10.1016/j.molcel.2014.03.014. View

Bogliolo M, Schuster B, Stoepker C, Derkunt B, Su Y, Raams A . Mutations in ERCC4, encoding the DNA-repair endonuclease XPF, cause Fanconi anemia. Am J Hum Genet. 2013; 92(5):800-6. PMC: 3644630. DOI: 10.1016/j.ajhg.2013.04.002. View

Kratz K, Schopf B, Kaden S, Sendoel A, Eberhard R, Lademann C . Deficiency of FANCD2-associated nuclease KIAA1018/FAN1 sensitizes cells to interstrand crosslinking agents. Cell. 2010; 142(1):77-88. DOI: 10.1016/j.cell.2010.06.022. View

Yamamura K, Ichihashi M, Hiramoto T, Ogoshi M, Nishioka K, Fujiwara Y . Clinical and photobiological characteristics of xeroderma pigmentosum complementation group F: a review of cases from Japan. Br J Dermatol. 1989; 121(4):471-80. DOI: 10.1111/j.1365-2133.1989.tb15514.x. View

Panier S, Maric M, Hewitt G, Mason-Osann E, Gali H, Dai A . SLX4IP Antagonizes Promiscuous BLM Activity during ALT Maintenance. Mol Cell. 2019; 76(1):27-43.e11. PMC: 6863466. DOI: 10.1016/j.molcel.2019.07.010. View

Van Wassenhove L, Mochly-Rosen D, Weinberg K . Aldehyde dehydrogenase 2 in aplastic anemia, Fanconi anemia and hematopoietic stem cells. Mol Genet Metab. 2016; 119(1-2):28-36. PMC: 5082284. DOI: 10.1016/j.ymgme.2016.07.004. View

Choi Y, Ryu K, Ko Y, Chae Y, Pelton J, Wemmer D . Biophysical characterization of the interaction domains and mapping of the contact residues in the XPF-ERCC1 complex. J Biol Chem. 2005; 280(31):28644-52. DOI: 10.1074/jbc.M501083200. View

Wood R . Mammalian nucleotide excision repair proteins and interstrand crosslink repair. Environ Mol Mutagen. 2010; 51(6):520-6. PMC: 3017513. DOI: 10.1002/em.20569. View

10.

Soulier J, Leblanc T, Larghero J, Dastot H, Shimamura A, Guardiola P . Detection of somatic mosaicism and classification of Fanconi anemia patients by analysis of the FA/BRCA pathway. Blood. 2004; 105(3):1329-36. DOI: 10.1182/blood-2004-05-1852. View

11.

Meetei A, Medhurst A, Ling C, Xue Y, Singh T, Bier P . A human ortholog of archaeal DNA repair protein Hef is defective in Fanconi anemia complementation group M. Nat Genet. 2005; 37(9):958-63. PMC: 2704909. DOI: 10.1038/ng1626. View

12.

Wan B, Yin J, Horvath K, Sarkar J, Chen Y, Wu J . SLX4 assembles a telomere maintenance toolkit by bridging multiple endonucleases with telomeres. Cell Rep. 2013; 4(5):861-9. PMC: 4334113. DOI: 10.1016/j.celrep.2013.08.017. View

13.

Knipscheer P, Raschle M, Smogorzewska A, Enoiu M, Ho T, Scharer O . The Fanconi anemia pathway promotes replication-dependent DNA interstrand cross-link repair. Science. 2009; 326(5960):1698-701. PMC: 2909596. DOI: 10.1126/science.1182372. View

14.

Heinrich M, Hoatlin M, Zigler A, Silvey K, Bakke A, Keeble W . DNA cross-linker-induced G2/M arrest in group C Fanconi anemia lymphoblasts reflects normal checkpoint function. Blood. 1998; 91(1):275-87. View

15.

Graf N, Ang W, Zhu G, Myint M, Lippard S . Role of endonucleases XPF and XPG in nucleotide excision repair of platinated DNA and cisplatin/oxaliplatin cytotoxicity. Chembiochem. 2011; 12(7):1115-23. PMC: 3081389. DOI: 10.1002/cbic.201000724. View

16.

Hinz J . Role of homologous recombination in DNA interstrand crosslink repair. Environ Mol Mutagen. 2010; 51(6):582-603. DOI: 10.1002/em.20577. View

17.

Rothfuss A, Grompe M . Repair kinetics of genomic interstrand DNA cross-links: evidence for DNA double-strand break-dependent activation of the Fanconi anemia/BRCA pathway. Mol Cell Biol. 2003; 24(1):123-34. PMC: 303365. DOI: 10.1128/MCB.24.1.123-134.2004. View

18.

Chen Z, Tran M, Tang M, Wang W, Gong Z, Chen J . Proteomic Analysis Reveals a Novel Mutator S (MutS) Partner Involved in Mismatch Repair Pathway. Mol Cell Proteomics. 2016; 15(4):1299-308. PMC: 4824856. DOI: 10.1074/mcp.M115.056093 . View

19.

Wang L, Gautier J . The Fanconi anemia pathway and ICL repair: implications for cancer therapy. Crit Rev Biochem Mol Biol. 2010; 45(5):424-39. PMC: 3108053. DOI: 10.3109/10409238.2010.502166. View

20.

Norris P, Hawk J, Avery J, Giannelli F . Xeroderma pigmentosum complementation group F in a non-Japanese patient. J Am Acad Dermatol. 1988; 18(5 Pt 2):1185-8. DOI: 10.1016/s0190-9622(88)70121-8. View