Current Understanding of RAD52 Functions: Fundamental and Therapeutic Insights
Abstract
:1. Introduction
2. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
- Sugiyama, T.; New, J.H.; Kowalczykowski, S.C. DNA annealing by RAD52 protein is stimulated by specific interaction with the complex of replication protein A and single-stranded DNA. Proc. Natl. Acad. Sci. USA 1998, 95, 6049–6054. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Stark, J.M.; Pierce, A.J.; Oh, J.; Pastink, A.; Jasin, M. Genetic steps of mammalian homologous repair with distinct mutagenic consequences. Mol. Cell Biol. 2004, 24, 9305–9316. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kan, Y.; Batada, N.N.; Hendrickson, E.A. Human somatic cells deficient for RAD52 are impaired for viral integration and compromised for most aspects of homology-directed repair. DNA Repair (Amst) 2017, 55, 64–75. [Google Scholar] [CrossRef] [PubMed]
- Stasiak, A.Z.; Larquet, E.; Stasiak, A.; Muller, S.; Engel, A.; Van Dyck, E.; West, S.C.; Egelman, E.H. The human Rad52 protein exists as a heptameric ring. Curr. Biol. 2000, 10, 337–340. [Google Scholar] [CrossRef] [Green Version]
- Kagawa, W.; Kagawa, A.; Saito, K.; Ikawa, S.; Shibata, T.; Kurumizaka, H.; Yokoyama, S. Identification of a second DNA binding site in the human Rad52 protein. J. Biol. Chem. 2008, 283, 24264–24273. [Google Scholar] [CrossRef] [Green Version]
- Altmannova, V.; Eckert-Boulet, N.; Arneric, M.; Kolesar, P.; Chaloupkova, R.; Damborsky, J.; Sung, P.; Zhao, X.; Lisby, M.; Krejci, L. Rad52 SUMOylation affects the efficiency of the DNA repair. Nucleic Acids Res. 2010, 38, 4708–4721. [Google Scholar] [CrossRef] [Green Version]
- Yasuda, T.; Kagawa, W.; Ogi, T.; Kato, T.A.; Suzuki, T.; Dohmae, N.; Takizawa, K.; Nakazawa, Y.; Genet, M.D.; Saotome, M.; et al. Novel function of HATs and HDACs in homologous recombination through acetylation of human RAD52 at double-strand break sites. PLoS Genet. 2018, 14, e1007277. [Google Scholar] [CrossRef]
- Toma, M.; Sullivan-Reed, K.; Sliwinski, T.; Skorski, T. RAD52 as a Potential Target for Synthetic Lethality-Based Anticancer Therapies. Cancers (Basel) 2019, 11, 1561. [Google Scholar] [CrossRef] [Green Version]
- Jalan, M.; Olsen, K.S.; Powell, S.N. Emerging Roles of RAD52 in Genome Maintenance. Cancers (Basel) 2019, 11, 1038. [Google Scholar] [CrossRef] [Green Version]
- Wu, X. Replication Stress Response Links RAD52 to Protecting Common Fragile Sites. Cancers (Basel) 2019, 11, 1467. [Google Scholar] [CrossRef] [Green Version]
- Franchet, C.; Hoffmann, J.S. When RAD52 Allows Mitosis to Accept Unscheduled DNA Synthesis. Cancers (Basel) 2019, 12, 26. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Malacaria, E.; Honda, M.; Franchitto, A.; Spies, M.; Pichierri, P. Physiological and Pathological Roles of RAD52 at DNA Replication Forks. Cancers (Basel) 2020, 12, 402. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hendrickson, E.A. RAD52: Viral Friend or Foe? Cancers (Basel) 2020, 12, 399. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Verma, P.; Dilley, R.L.; Zhang, T.; Gyparaki, M.T.; Li, Y.; Greenberg, R.A. RAD52 and SLX4 act nonepistatically to ensure telomere stability during alternative telomere lengthening. Genes Dev. 2019, 33, 221–235. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zhang, J.M.; Yadav, T.; Ouyang, J.; Lan, L.; Zou, L. Alternative Lengthening of Telomeres through Two Distinct Break-Induced Replication Pathways. Cell Rep. 2019, 26, 955–968.e953. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bhowmick, R.; Minocherhomji, S.; Hickson, I.D. RAD52 Facilitates Mitotic DNA Synthesis Following Replication Stress. Mol. Cell 2016, 64, 1117–1126. [Google Scholar] [CrossRef]
- Murfuni, I.; Basile, G.; Subramanyam, S.; Malacaria, E.; Bignami, M.; Spies, M.; Franchitto, A.; Pichierri, P. Survival of the replication checkpoint deficient cells requires MUS81-RAD52 function. PLoS Genet. 2013, 9, e1003910. [Google Scholar] [CrossRef] [Green Version]
- Mijic, S.; Zellweger, R.; Chappidi, N.; Berti, M.; Jacobs, K.; Mutreja, K.; Ursich, S.; Ray Chaudhuri, A.; Nussenzweig, A.; Janscak, P.; et al. Replication fork reversal triggers fork degradation in BRCA2-defective cells. Nat. Commun. 2017, 8, 859. [Google Scholar] [CrossRef]
- Murfuni, I.; Basile, G.; Subramanyam, S.; Malacaria, E.; Bignami, M.; Spies, M.; Franchitto, A.; Pichierri, P. Author Correction: Rad52 prevents excessive replication fork reversal and protects from nascent strand degradation. Nat. Commun. 2019, 10, 2023. [Google Scholar]
- Isakoff, S.J.; Puhalla, S.; Domchek, S.M.; Friedlander, M.; Kaufman, B.; Robson, M.; Telli, M.L.; Dieras, V.; Han, H.S.; Garber, J.E.; et al. A randomized Phase II study of veliparib with temozolomide or carboplatin/paclitaxel versus placebo with carboplatin/paclitaxel in BRCA1/2 metastatic breast cancer: design and rationale. Future Oncol. 2017, 13, 307–320. [Google Scholar] [CrossRef] [Green Version]
- Bergoglio, V.; Boyer, A.S.; Walsh, E.; Naim, V.; Legube, G.; Lee, M.Y.; Rey, L.; Rosselli, F.; Cazaux, C.; Eckert, K.A.; et al. DNA synthesis by Pol eta promotes fragile site stability by preventing under-replicated DNA in mitosis. J. Cell Biol. 2013, 201, 395–408. [Google Scholar] [CrossRef] [Green Version]
- Minocherhomji, S.; Ying, S.; Bjerregaard, V.A.; Bursomanno, S.; Aleliunaite, A.; Wu, W.; Mankouri, H.W.; Shen, H.; Liu, Y.; Hickson, I.D. Replication stress activates DNA repair synthesis in mitosis. Nature 2015, 528, 286–290. [Google Scholar] [CrossRef]
- Ozer, O.; Bhowmick, R.; Liu, Y.; Hickson, I.D. Human cancer cells utilize mitotic DNA synthesis to resist replication stress at telomeres regardless of their telomere maintenance mechanism. Oncotarget 2018, 9, 15836–15846. [Google Scholar] [CrossRef]
- Lukas, C.; Savic, V.; Bekker-Jensen, S.; Doil, C.; Neumann, B.; Pedersen, R.S.; Grofte, M.; Chan, K.L.; Hickson, I.D.; Bartek, J.; et al. 53BP1 nuclear bodies form around DNA lesions generated by mitotic transmission of chromosomes under replication stress. Nat. Cell Biol. 2011, 13, 243–253. [Google Scholar] [CrossRef]
- Lok, B.H.; Powell, S.N. Molecular pathways: understanding the role of Rad52 in homologous recombination for therapeutic advancement. Clin. Cancer Res. 2012, 18, 6400–6406. [Google Scholar] [CrossRef] [Green Version]
- Durkin, S.G.; Glover, T.W. Chromosome fragile sites. Annu. Rev. Genet. 2007, 41, 169–192. [Google Scholar] [CrossRef]
- Gorgoulis, V.G.; Vassiliou, L.V.; Karakaidos, P.; Zacharatos, P.; Kotsinas, A.; Liloglou, T.; Venere, M.; Ditullio, R.A., Jr.; Kastrinakis, N.G.; Levy, B.; et al. Activation of the DNA damage checkpoint and genomic instability in human precancerous lesions. Nature 2005, 434, 907–913. [Google Scholar] [CrossRef] [PubMed]
- Tsantoulis, P.K.; Kotsinas, A.; Sfikakis, P.P.; Evangelou, K.; Sideridou, M.; Levy, B.; Mo, L.; Kittas, C.; Wu, X.R.; Papavassiliou, A.G.; et al. Oncogene-induced replication stress preferentially targets common fragile sites in preneoplastic lesions. A genome-wide study. Oncogene 2008, 27, 3256–3264. [Google Scholar] [CrossRef] [Green Version]
- Bartkova, J.; Horejsi, Z.; Koed, K.; Kramer, A.; Tort, F.; Zieger, K.; Guldberg, P.; Sehested, M.; Nesland, J.M.; Lukas, C.; et al. DNA damage response as a candidate anti-cancer barrier in early human tumorigenesis. Nature 2005, 434, 864–870. [Google Scholar] [CrossRef] [PubMed]
- Wang, H.; Li, S.; Oaks, J.; Ren, J.; Li, L.; Wu, X. The concerted roles of FANCM and Rad52 in the protection of common fragile sites. Nat. Commun. 2018, 9, 2791. [Google Scholar] [CrossRef] [PubMed]
- Mazina, O.M.; Keskin, H.; Hanamshet, K.; Storici, F.; Mazin, A.V. Rad52 Inverse Strand Exchange Drives RNA-Templated DNA Double-Strand Break Repair. Mol. Cell 2017, 67, 19–29.e13. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ma, C.J.; Kwon, Y.; Sung, P.; Greene, E.C. Human RAD52 interactions with replication protein A and the RAD51 presynaptic complex. J. Biol. Chem. 2017, 292, 11702–11713. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Liu, J.; Heyer, W.D. Who’s who in human recombination: BRCA2 and RAD52. Proc. Natl. Acad. Sci. USA 2011, 108, 441–442. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Li, S.; Lu, H.; Wang, Z.; Hu, Q.; Wang, H.; Xiang, R.; Chiba, T.; Wu, X. ERCC1/XPF Is Important for Repair of DNA Double-Strand Breaks Containing Secondary Structures. iScience 2019, 16, 63–78. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Motycka, T.A.; Bessho, T.; Post, S.M.; Sung, P.; Tomkinson, A.E. Physical and functional interaction between the XPF/ERCC1 endonuclease and hRad52. J. Biol. Chem. 2004, 279, 13634–13639. [Google Scholar] [CrossRef] [Green Version]
- Naim, V.; Wilhelm, T.; Debatisse, M.; Rosselli, F. ERCC1 and MUS81-EME1 promote sister chromatid separation by processing late replication intermediates at common fragile sites during mitosis. Nat. Cell Biol. 2013, 15, 1008–1015. [Google Scholar] [CrossRef]
- Hengel, S.R.; Malacaria, E.; Folly da Silva Constantino, L.; Bain, F.E.; Diaz, A.; Koch, B.G.; Yu, L.; Wu, M.; Pichierri, P.; Spies, M.A.; et al. Small-molecule inhibitors identify the RAD52-ssDNA interaction as critical for recovery from replication stress and for survival of BRCA2 deficient cells. Elife 2016, 5, e14740. [Google Scholar] [CrossRef]
- Feng, Z.; Scott, S.P.; Bussen, W.; Sharma, G.G.; Guo, G.; Pandita, T.K.; Powell, S.N. Rad52 inactivation is synthetically lethal with BRCA2 deficiency. Proc. Natl. Acad. Sci. USA 2011, 108, 686–691. [Google Scholar] [CrossRef] [Green Version]
- Lok, B.H.; Carley, A.C.; Tchang, B.; Powell, S.N. RAD52 inactivation is synthetically lethal with deficiencies in BRCA1 and PALB2 in addition to BRCA2 through RAD51-mediated homologous recombination. Oncogene 2013, 32, 3552–3558. [Google Scholar] [CrossRef] [Green Version]
- Sotiriou, S.K.; Kamileri, I.; Lugli, N.; Evangelou, K.; Da-Re, C.; Huber, F.; Padayachy, L.; Tardy, S.; Nicati, N.L.; Barriot, S.; et al. Mammalian RAD52 Functions in Break-Induced Replication Repair of Collapsed DNA Replication Forks. Mol. Cell 2016, 64, 1127–1134. [Google Scholar] [CrossRef] [Green Version]
- Doe, C.L.; Osman, F.; Dixon, J.; Whitby, M.C. DNA repair by a Rad22-Mus81-dependent pathway that is independent of Rhp51. Nucleic Acids Res. 2004, 32, 5570–5581. [Google Scholar] [CrossRef] [Green Version]
- Storici, F.; Bebenek, K.; Kunkel, T.A.; Gordenin, D.A.; Resnick, M.A. RNA-templated DNA repair. Nature 2007, 447, 338–341. [Google Scholar] [CrossRef]
- Stirling, P.C.; Chan, Y.A.; Minaker, S.W.; Aristizabal, M.J.; Barrett, I.; Sipahimalani, P.; Kobor, M.S.; Hieter, P. R-loop-mediated genome instability in mRNA cleavage and polyadenylation mutants. Genes Dev. 2012, 26, 163–175. [Google Scholar] [CrossRef] [Green Version]
- Weller, S.K.; Sawitzke, J.A. Recombination promoted by DNA viruses: phage lambda to herpes simplex virus. Annu. Rev. Microbiol. 2014, 68, 237–258. [Google Scholar] [CrossRef] [Green Version]
- Lau, A.; Kanaar, R.; Jackson, S.P.; O’Connor, M.J. Suppression of retroviral infection by the RAD52 DNA repair protein. EMBO J. 2004, 23, 3421–3429. [Google Scholar] [CrossRef] [Green Version]
- Li, L.; Olvera, J.M.; Yoder, K.E.; Mitchell, R.S.; Butler, S.L.; Lieber, M.; Martin, S.L.; Bushman, F.D. Role of the non-homologous DNA end joining pathway in the early steps of retroviral infection. EMBO J. 2001, 20, 3272–3281. [Google Scholar] [CrossRef] [PubMed]
- Karanam, K.; Kafri, R.; Loewer, A.; Lahav, G. Quantitative live cell imaging reveals a gradual shift between DNA repair mechanisms and a maximal use of HR in mid S phase. Mol. Cell 2012, 47, 320–329. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Audebert, M.; Salles, B.; Calsou, P. Involvement of poly(ADP-ribose) polymerase-1 and XRCC1/DNA ligase III in an alternative route for DNA double-strand breaks rejoining. J. Biol. Chem. 2004, 279, 55117–55126. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wang, M.; Wu, W.; Wu, W.; Rosidi, B.; Zhang, L.; Wang, H.; Iliakis, G. PARP-1 and Ku compete for repair of DNA double strand breaks by distinct NHEJ pathways. Nucleic Acids Res. 2006, 34, 6170–6182. [Google Scholar] [CrossRef]
- Cramer, K.; Nieborowska-Skorska, M.; Koptyra, M.; Slupianek, A.; Penserga, E.T.; Eaves, C.J.; Aulitzky, W.; Skorski, T. BCR/ABL and other kinases from chronic myeloproliferative disorders stimulate single-strand annealing, an unfaithful DNA double-strand break repair. Cancer Res. 2008, 68, 6884–6888. [Google Scholar] [CrossRef] [Green Version]
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Gottifredi, V.; Wiesmüller, L. Current Understanding of RAD52 Functions: Fundamental and Therapeutic Insights. Cancers 2020, 12, 705. https://doi.org/10.3390/cancers12030705
Gottifredi V, Wiesmüller L. Current Understanding of RAD52 Functions: Fundamental and Therapeutic Insights. Cancers. 2020; 12(3):705. https://doi.org/10.3390/cancers12030705
Chicago/Turabian StyleGottifredi, Vanesa, and Lisa Wiesmüller. 2020. "Current Understanding of RAD52 Functions: Fundamental and Therapeutic Insights" Cancers 12, no. 3: 705. https://doi.org/10.3390/cancers12030705
APA StyleGottifredi, V., & Wiesmüller, L. (2020). Current Understanding of RAD52 Functions: Fundamental and Therapeutic Insights. Cancers, 12(3), 705. https://doi.org/10.3390/cancers12030705