Regulation of Double-strand Break-induced Mammalian Homologous Recombination by UBL1, a RAD51-interacting Protein

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2000 Feb 10

PMID 10666456

Citations 21

Authors

W Li

B Hesabi

A Babbo

C Pacione

J Liu

D J Chen

J A Nickoloff

Z Shen

Affiliations

Soon will be listed here.

Abstract

Mammalian RAD51 protein plays essential roles in DNA homologous recombination, DNA repair and cell proliferation. RAD51 activities are regulated by its associated proteins. It was previously reported that a ubiquitin-like protein, UBL1, associates with RAD51 in the yeast two-hybrid system. One function of UBL1 is to covalently conjugate with target proteins and thus modify their function. In the present study we found that non-conjugated UBL1 forms a complex with RAD51 and RAD52 proteins in human cells. Overexpression of UBL1 down-regulates DNA double-strand break-induced homologous recombination in CHO cells and reduces cellular resistance to ionizing radiation in HT1080 cells. With or without overexpressed UBL1, most homologous recombination products arise by gene conversion. However, overexpression of UBL1 reduces the fraction of bidirectional gene conversion tracts. Overexpression of a mutant UBL1 that is incapable of being conjugated retains the ability to inhibit homologous recombination. These results suggest a regulatory role for UBL1 in homologous recombination.

Citing Articles

TOPORS-mediated RAD51 SUMOylation facilitates homologous recombination repair.

Hariharasudhan G, Jeong S, Kim M, Jung S, Seo G, Moon J Nucleic Acids Res. 2022; 50(3):1501-1516.

PMID: 35061896 PMC: 8860612. DOI: 10.1093/nar/gkac009.

Advances in SUMO-based regulation of homologous recombination.

Dhingra N, Zhao X Curr Opin Genet Dev. 2021; 71:114-119.

PMID: 34333341 PMC: 8671156. DOI: 10.1016/j.gde.2021.07.007.

Depletion of DNA damage binding protein 2 sensitizes triple-negative breast cancer cells to poly ADP-ribose polymerase inhibition by destabilizing Rad51.

Zhao L, Si C, Yu Y, Lu J, Zhuang Y Cancer Sci. 2019; 110(11):3543-3552.

PMID: 31541611 PMC: 6825009. DOI: 10.1111/cas.14201.

Sumoylation-independent activation of Calcineurin-NFAT-signaling via SUMO2 mediates cardiomyocyte hypertrophy.

Bernt A, Rangrez A, Eden M, Jungmann A, Katz S, Rohr C Sci Rep. 2016; 6:35758.

PMID: 27767176 PMC: 5073337. DOI: 10.1038/srep35758.

Small ubiquitin-like modifier (SUMO) isoforms and conjugation-independent function in DNA double-strand break repair pathways.

Hu Y, Parvin J J Biol Chem. 2014; 289(31):21289-95.

PMID: 24966330 PMC: 4118090. DOI: 10.1074/jbc.C114.582122.

References

Golub E, Kovalenko O, Gupta R, Ward D, Radding C . Interaction of human recombination proteins Rad51 and Rad54. Nucleic Acids Res. 1997; 25(20):4106-10. PMC: 147015. DOI: 10.1093/nar/25.20.4106. View

Taghian D, Nickoloff J . Chromosomal double-strand breaks induce gene conversion at high frequency in mammalian cells. Mol Cell Biol. 1997; 17(11):6386-93. PMC: 232490. DOI: 10.1128/MCB.17.11.6386. View

Johnson E, Blobel G . Ubc9p is the conjugating enzyme for the ubiquitin-like protein Smt3p. J Biol Chem. 1997; 272(43):26799-802. DOI: 10.1074/jbc.272.43.26799. View

Peelen T, van Vliet M, van Eijk R, Olmer R, Drusedau M, Hogervorst F . BRCA1 genomic deletions are major founder mutations in Dutch breast cancer patients. Nat Genet. 1997; 17(3):341-5. DOI: 10.1038/ng1197-341. View

Sung P . Function of yeast Rad52 protein as a mediator between replication protein A and the Rad51 recombinase. J Biol Chem. 1997; 272(45):28194-7. DOI: 10.1074/jbc.272.45.28194. View

Gong L, Kamitani T, Fujise K, Caskey L, Yeh E . Preferential interaction of sentrin with a ubiquitin-conjugating enzyme, Ubc9. J Biol Chem. 1997; 272(45):28198-201. DOI: 10.1074/jbc.272.45.28198. View

Saitoh H, Pu R, Dasso M . SUMO-1: wrestling with a new ubiquitin-related modifier. Trends Biochem Sci. 1997; 22(10):374-6. DOI: 10.1016/s0968-0004(97)01102-x. View

Buchhop S, Gibson M, Wang X, Wagner P, Sturzbecher H, Harris C . Interaction of p53 with the human Rad51 protein. Nucleic Acids Res. 1997; 25(19):3868-74. PMC: 146972. DOI: 10.1093/nar/25.19.3868. View

Xia S, Shammas M, Shmookler Reis R . Elevated recombination in immortal human cells is mediated by HsRAD51 recombinase. Mol Cell Biol. 1997; 17(12):7151-8. PMC: 232572. DOI: 10.1128/MCB.17.12.7151. View

10.

Desterro J, Thomson J, Hay R . Ubch9 conjugates SUMO but not ubiquitin. FEBS Lett. 1997; 417(3):297-300. DOI: 10.1016/s0014-5793(97)01305-7. View

11.

Sternsdorf T, Jensen K, Will H . Evidence for covalent modification of the nuclear dot-associated proteins PML and Sp100 by PIC1/SUMO-1. J Cell Biol. 1998; 139(7):1621-34. PMC: 2132645. DOI: 10.1083/jcb.139.7.1621. View

12.

Saitoh H, Sparrow D, Shiomi T, Pu R, Nishimoto T, Mohun T . Ubc9p and the conjugation of SUMO-1 to RanGAP1 and RanBP2. Curr Biol. 1998; 8(2):121-4. DOI: 10.1016/s0960-9822(98)70044-2. View

13.

Muller S, Matunis M, Dejean A . Conjugation with the ubiquitin-related modifier SUMO-1 regulates the partitioning of PML within the nucleus. EMBO J. 1998; 17(1):61-70. PMC: 1170358. DOI: 10.1093/emboj/17.1.61. View

14.

Mahajan R, Gerace L, Melchior F . Molecular characterization of the SUMO-1 modification of RanGAP1 and its role in nuclear envelope association. J Cell Biol. 1998; 140(2):259-70. PMC: 2132567. DOI: 10.1083/jcb.140.2.259. View

15.

Benson F, Baumann P, West S . Synergistic actions of Rad51 and Rad52 in recombination and DNA repair. Nature. 1998; 391(6665):401-4. DOI: 10.1038/34937. View

16.

Thompson L, Schild D . The contribution of homologous recombination in preserving genome integrity in mammalian cells. Biochimie. 1999; 81(1-2):87-105. DOI: 10.1016/s0300-9084(99)80042-x. View

17.

Chen G, Yuan S, Liu W, Xu Y, Trujillo K, Song B . Radiation-induced assembly of Rad51 and Rad52 recombination complex requires ATM and c-Abl. J Biol Chem. 1999; 274(18):12748-52. DOI: 10.1074/jbc.274.18.12748. View

18.

Van Dyck E, Stasiak A, Stasiak A, West S . Binding of double-strand breaks in DNA by human Rad52 protein. Nature. 1999; 398(6729):728-31. DOI: 10.1038/19560. View

19.

Thacker J . A surfeit of RAD51-like genes?. Trends Genet. 1999; 15(5):166-8. DOI: 10.1016/s0168-9525(99)01733-3. View

20.

Liu Q, Jin C, Liao X, Shen Z, Chen D, Chen Y . The binding interface between an E2 (UBC9) and a ubiquitin homologue (UBL1). J Biol Chem. 1999; 274(24):16979-87. DOI: 10.1074/jbc.274.24.16979. View