Targeting DNA-Protein Crosslinks Post-Translational Modifications

Overview

Journal Front Mol Biosci

Specialty Biology

Date 2022 Jul 21

PMID 35860355

Authors

Xueyuan Leng

Julien P Duxin

Affiliations

Soon will be listed here.

Abstract

Covalent binding of proteins to DNA forms DNA-protein crosslinks (DPCs), which represent cytotoxic DNA lesions that interfere with essential processes such as DNA replication and transcription. Cells possess different enzymatic activities to counteract DPCs. These include enzymes that degrade the adducted proteins, resolve the crosslinks, or incise the DNA to remove the crosslinked proteins. An important question is how DPCs are sensed and targeted for removal the most suited pathway. Recent advances have shown the inherent role of DNA replication in triggering DPC removal by proteolysis. However, DPCs are also efficiently sensed and removed in the absence of DNA replication. In either scenario, post-translational modifications (PTMs) on DPCs play essential and versatile roles in orchestrating the repair routes. In this review, we summarize the current knowledge of the mechanisms that trigger DPC removal PTMs, focusing on ubiquitylation, small ubiquitin-related modifier (SUMO) conjugation (SUMOylation), and poly (ADP-ribosyl)ation (PARylation). We also briefly discuss the current knowledge gaps and emerging hypotheses in the field.

Citing Articles

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References

Zhang H, Tomida A, Koshimizu R, Ogiso Y, Lei S, Tsuruo T . Cullin 3 promotes proteasomal degradation of the topoisomerase I-DNA covalent complex. Cancer Res. 2004; 64(3):1114-21. DOI: 10.1158/0008-5472.can-03-2858. View

Huang J, Zhou Q, Gao M, Nowsheen S, Zhao F, Kim W . Tandem Deubiquitination and Acetylation of SPRTN Promotes DNA-Protein Crosslink Repair and Protects against Aging. Mol Cell. 2020; 79(5):824-835.e5. PMC: 7484104. DOI: 10.1016/j.molcel.2020.06.027. View

Desai S, Liu L, DArpa P . Ubiquitin-dependent destruction of topoisomerase I is stimulated by the antitumor drug camptothecin. J Biol Chem. 1997; 272(39):24159-64. DOI: 10.1074/jbc.272.39.24159. View

Alchanati I, Teicher C, Cohen G, Shemesh V, Barr H, Nakache P . The E3 ubiquitin-ligase Bmi1/Ring1A controls the proteasomal degradation of Top2alpha cleavage complex - a potentially new drug target. PLoS One. 2009; 4(12):e8104. PMC: 2779455. DOI: 10.1371/journal.pone.0008104. View

Reinking H, Kang H, Gotz M, Li H, Kieser A, Zhao S . DNA Structure-Specific Cleavage of DNA-Protein Crosslinks by the SPRTN Protease. Mol Cell. 2020; 80(1):102-113.e6. PMC: 7534798. DOI: 10.1016/j.molcel.2020.08.003. View

Barker S, Weinfeld M, Zheng J, Li L, Murray D . Identification of mammalian proteins cross-linked to DNA by ionizing radiation. J Biol Chem. 2005; 280(40):33826-38. DOI: 10.1074/jbc.M502477200. View

Mao Y, Desai S, Ting C, Hwang J, Liu L . 26 S proteasome-mediated degradation of topoisomerase II cleavable complexes. J Biol Chem. 2001; 276(44):40652-8. DOI: 10.1074/jbc.M104009200. View

Krastev D, Li S, Sun Y, Wicks A, Hoslett G, Weekes D . The ubiquitin-dependent ATPase p97 removes cytotoxic trapped PARP1 from chromatin. Nat Cell Biol. 2022; 24(1):62-73. PMC: 8760077. DOI: 10.1038/s41556-021-00807-6. View

Lecona E, Rodriguez-Acebes S, Specks J, Lopez-Contreras A, Ruppen I, Murga M . USP7 is a SUMO deubiquitinase essential for DNA replication. Nat Struct Mol Biol. 2016; 23(4):270-7. PMC: 4869841. DOI: 10.1038/nsmb.3185. View

10.

Steinacher R, Osman F, Lorenz A, Bryer C, Whitby M . Slx8 removes Pli1-dependent protein-SUMO conjugates including SUMOylated topoisomerase I to promote genome stability. PLoS One. 2013; 8(8):e71960. PMC: 3735562. DOI: 10.1371/journal.pone.0071960. View

11.

Mullen J, Chen C, Brill S . Wss1 is a SUMO-dependent isopeptidase that interacts genetically with the Slx5-Slx8 SUMO-targeted ubiquitin ligase. Mol Cell Biol. 2010; 30(15):3737-48. PMC: 2916399. DOI: 10.1128/MCB.01649-09. View

12.

Franz A, Valledor P, Ubieto-Capella P, Pilger D, Galarreta A, Lafarga V . USP7 and VCP define the SUMO/Ubiquitin landscape at the DNA replication fork. Cell Rep. 2021; 37(2):109819. PMC: 8527565. DOI: 10.1016/j.celrep.2021.109819. View

13.

Prasad R, Horton J, Dai D, Wilson S . Repair pathway for PARP-1 DNA-protein crosslinks. DNA Repair (Amst). 2018; 73:71-77. PMC: 6312470. DOI: 10.1016/j.dnarep.2018.11.004. View

14.

Saha S, Sun Y, Huang S, Baechler S, Pongor L, Agama K . DNA and RNA Cleavage Complexes and Repair Pathway for TOP3B RNA- and DNA-Protein Crosslinks. Cell Rep. 2020; 33(13):108569. PMC: 7859927. DOI: 10.1016/j.celrep.2020.108569. View

15.

Yip M, Bodnar N, Rapoport T . Ddi1 is a ubiquitin-dependent protease. Proc Natl Acad Sci U S A. 2020; 117(14):7776-7781. PMC: 7149228. DOI: 10.1073/pnas.1902298117. View

16.

Malanga M, Althaus F . Poly(ADP-ribose) reactivates stalled DNA topoisomerase I and Induces DNA strand break resealing. J Biol Chem. 2003; 279(7):5244-8. DOI: 10.1074/jbc.C300437200. View

17.

Inano S, Sato K, Katsuki Y, Kobayashi W, Tanaka H, Nakajima K . RFWD3-Mediated Ubiquitination Promotes Timely Removal of Both RPA and RAD51 from DNA Damage Sites to Facilitate Homologous Recombination. Mol Cell. 2017; 66(5):622-634.e8. DOI: 10.1016/j.molcel.2017.04.022. View

18.

Fielden J, Wiseman K, Torrecilla I, Li S, Hume S, Chiang S . TEX264 coordinates p97- and SPRTN-mediated resolution of topoisomerase 1-DNA adducts. Nat Commun. 2020; 11(1):1274. PMC: 7062751. DOI: 10.1038/s41467-020-15000-w. View

19.

Ma C, Su B, Maciaszek A, Fan H, Guga P, Jayaram M . A Flp-SUMO hybrid recombinase reveals multi-layered copy number control of a selfish DNA element through post-translational modification. PLoS Genet. 2019; 15(6):e1008193. PMC: 6594588. DOI: 10.1371/journal.pgen.1008193. View

20.

Aravind L, Koonin E . SAP - a putative DNA-binding motif involved in chromosomal organization. Trends Biochem Sci. 2000; 25(3):112-4. DOI: 10.1016/s0968-0004(99)01537-6. View