Dual roles of UFMylation on stalling fork stability

Yisui Xia, Wenpeng Liu, Huiqiang Lou

Genome Instability & Disease ›› 2024, Vol. 5 ›› Issue (3) : 127-130. DOI: 10.1007/s42764-024-00129-5
Commentary

Dual roles of UFMylation on stalling fork stability

Author information +
History +

Abstract

The mechanism governing the stabilization of the replication fork under replication stress is pivotal for maintaining genomic integrity and cellular viability. In this context, the safeguard factors BRCA1/2 and nucleases engage in a regulatory equilibrium, modulating the extent of nascent strand end resection—a process vital for replication fork stabilization under stress and for fork restart upon stress released. The recruitment dynamics of these nucleases, however, remain to be elucidated. Recent two independent studies by Gong et al. and Tian et al. have demonstrated that ubiquitin-like modification UFMylation employs dual pathways to facilitate the recruitment of nuclease MRE11, integral to the fork reversal mechanism. These revelations uncover novel roles of UFMylation in genome stability and provide guidance in identifying novel targets for treating BRCA1/2-mutated tumors.

Keywords

DNA replication / Replication stress / Fork stability / Genome stability / Nuclease / Post-translational modifications

Cite this article

Download citation ▾
Yisui Xia, Wenpeng Liu, Huiqiang Lou. Dual roles of UFMylation on stalling fork stability. Genome Instability & Disease, 2024, 5(3): 127‒130 https://doi.org/10.1007/s42764-024-00129-5

References

[]
Amunugama R, Willcox S, Wu RA, Abdullah UB, El-Sagheer AH, Brown T, McHugh PJ, Griffith JD, Walter JC. Replication fork reversal during DNA interstrand Crosslink Repair requires CMG unloading. Cell Rep, 2018, 23: 3419-3428, pmcid: 6086610
CrossRef Pubmed Google scholar
[]
Berti M, Cortez D, Lopes M. The plasticity of DNA replication forks in response to clinically relevant genotoxic stress. Nature Reviews Molecular Cell Biology, 2020, 21: 633-651,
CrossRef Pubmed Google scholar
[]
Cong K, Cantor SB. Exploiting replication gaps for cancer therapy. Molecular Cell, 2022, 82: 2363-2369, pmcid: 9271608
CrossRef Pubmed Google scholar
[]
Cortez D. Replication-coupled DNA repair. Molecular Cell, 2019, 74: 866-876, pmcid: 6557297
CrossRef Pubmed Google scholar
[]
Gong Y, Wang Z, Zong W, Shi R, Sun W, Wang S, Peng B, Takeda S, Wang ZQ, Xu X. PARP1 UFMylation ensures the stability of stalled replication forks. Proc Natl Acad Sci U S A, 2024, 121: e2322520121, pmcid: 11066985
CrossRef Pubmed Google scholar
[]
Hanzlikova H, Kalasova I, Demin AA, Pennicott LE, Cihlarova Z, Caldecott KW. The importance of poly(ADP-Ribose) polymerase as a Sensor of Unligated Okazaki fragments during DNA replication. Molecular Cell, 2018, 71: 319-331e313, pmcid: 6060609
CrossRef Pubmed Google scholar
[]
Hashimoto Y, Ray Chaudhuri A, Lopes M, Costanzo V. Rad51 protects nascent DNA from Mre11-dependent degradation and promotes continuous DNA synthesis. Nature Structural & Molecular Biology, 2010, 17: 1305-1311,
CrossRef Google scholar
[]
Kavlashvili T, Liu W, Mohamed TM, Cortez D, Dewar JM. Replication fork uncoupling causes nascent strand degradation and fork reversal. Nature Structural & Molecular Biology, 2023, 30: 115-124,
CrossRef Google scholar
[]
Lee L, Perez Oliva AB, Martinez-Balsalobre E, Churikov D, Peter J, Rahmouni D, Audoly G, Azzoni V, Audebert S, Camoin L, et al.. UFMylation of MRE11 is essential for telomere length maintenance and hematopoietic stem cell survival. Science Advances, 2021, 7: eabc7371, pmcid: 8462904
CrossRef Pubmed Google scholar
[]
Lemacon D, Jackson J, Quinet A, Brickner JR, Li S, Yazinski S, You Z, Ira G, Zou L, Mosammaparast N, Vindigni A. MRE11 and EXO1 nucleases degrade reversed forks and elicit MUS81-dependent fork rescue in BRCA2-deficient cells. Nature Communications, 2017, 8: 860, pmcid: 5643552
CrossRef Pubmed Google scholar
[]
Lim PX, Zaman M, Feng W, Jasin M. BRCA2 promotes genomic integrity and therapy resistance primarily through its role in homology-directed repair. Molecular Cell, 2024, 84: 447-462e410,
CrossRef Pubmed Google scholar
[]
Liu, W., Krishnamoorthy, A., Zhao, R., & Cortez, D. (2020). Two replication fork remodeling pathways generate nuclease substrates for distinct fork protection factors. Science Advances, 6. https://doi.org/10.1126/sciadv.abc3598.
[]
Liu W, Saito Y, Jackson J, Bhowmick R, Kanemaki MT, Vindigni A, Cortez D. RAD51 bypasses the CMG helicase to promote replication fork reversal. Science, 2023, 380: 382-387, pmcid: 10302453
CrossRef Pubmed Google scholar
[]
Lopes M, Foiani M, Sogo JM. Multiple mechanisms control chromosome integrity after replication fork uncoupling and restart at irreparable UV lesions. Molecular Cell, 2006, 21: 15-27,
CrossRef Pubmed Google scholar
[]
Makhlouf L, Peter JJ, Magnussen HM, Thakur R, Millrine D, Minshull TC, Harrison G, Varghese J, Lamoliatte F, Foglizzo M, et al.. The UFM1 E3 ligase recognizes and releases 60S ribosomes from ER translocons. Nature, 2024, 627: 437-444, pmcid: 10937380
CrossRef Pubmed Google scholar
[]
Peter JJ, Magnussen HM, DaRosa PA, Millrine D, Matthews SP, Lamoliatte F, Sundaramoorthy R, Kopito RR, Kulathu Y. A non-canonical scaffold-type E3 ligase complex mediates protein UFMylation. Embo Journal, 2022, 41: e111015, pmcid: 9627666
CrossRef Pubmed Google scholar
[]
Petropoulos M, Karamichali A, Rossetti GG, Freudenmann A, Iacovino LG, Dionellis VS, Sotiriou SK, Halazonetis TD. Transcription-replication conflicts underlie sensitivity to PARP inhibitors. Nature, 2024, 628: 433-441, pmcid: 11006605
CrossRef Pubmed Google scholar
[]
Ray Chaudhuri A, Callen E, Ding X, Gogola E, Duarte AA, Lee JE, Wong N, Lafarga V, Calvo JA, Panzarino NJ, et al.. Replication fork stability confers chemoresistance in BRCA-deficient cells. Nature, 2016, 535: 382-387,
CrossRef Pubmed Google scholar
[]
Rondinelli B, Gogola E, Yucel H, Duarte AA, van de Ven M, van der Sluijs R, Konstantinopoulos PA, Jonkers J, Ceccaldi R, Rottenberg S, D’Andrea AD. EZH2 promotes degradation of stalled replication forks by recruiting MUS81 through histone H3 trimethylation. Nature Cell Biology, 2017, 19: 1371-1378,
CrossRef Pubmed Google scholar
[]
Saldivar JC, Cortez D, Cimprich KA. The essential kinase ATR: Ensuring faithful duplication of a challenging genome. Nature Reviews Molecular Cell Biology, 2017, 18: 622-636, pmcid: 5796526
CrossRef Pubmed Google scholar
[]
Schlacher K, Christ N, Siaud N, Egashira A, Wu H, Jasin M. Double-strand break repair-independent role for BRCA2 in blocking stalled replication fork degradation by MRE11. Cell, 2011, 145: 529-542, pmcid: 3261725
CrossRef Pubmed Google scholar
[]
Schlacher K, Wu H, Jasin M. A distinct replication fork protection pathway connects fanconi anemia tumor suppressors to RAD51-BRCA1/2. Cancer Cell, 2012, 22: 106-116, pmcid: 3954744
CrossRef Pubmed Google scholar
[]
Thakar T, Moldovan GL. The emerging determinants of replication fork stability. Nucleic Acids Research, 2021, 49: 7224-7238, pmcid: 8287955
CrossRef Pubmed Google scholar
[]
Thangavel S, Berti M, Levikova M, Pinto C, Gomathinayagam S, Vujanovic M, Zellweger R, Moore H, Lee EH, Hendrickson EA, et al.. DNA2 drives processing and restart of reversed replication forks in human cells. Journal of Cell Biology, 2015, 208: 545-562, pmcid: 4347643
CrossRef Pubmed Google scholar
[]
Tian T, Chen J, Zhao H, Li Y, Xia F, Huang J, Han J, Liu T. UFL1 triggers replication fork degradation by MRE11 in BRCA1/2-deficient cells. Nature Chemical Biology, 2024,
CrossRef Pubmed Google scholar
[]
Ying S, Hamdy FC, Helleday T. Mre11-dependent degradation of stalled DNA replication forks is prevented by BRCA2 and PARP1. Cancer Research, 2012, 72: 2814-2821,
CrossRef Pubmed Google scholar
[]
Zellweger R, Dalcher D, Mutreja K, Berti M, Schmid JA, Herrador R, Vindigni A, Lopes M. Rad51-mediated replication fork reversal is a global response to genotoxic treatments in human cells. Journal of Cell Biology, 2015, 208: 563-579, pmcid: 4347635
CrossRef Pubmed Google scholar
Funding
National Natural Science Foundation of China(32161133015); Key Technologies Research and Development Program of Anhui Province(2019YFA0903900)

Accesses

Citations

Detail

Sections
Recommended

/