Role of PSO genes in repair of DNA damage of Saccharomyces cerevisiae

Brendel, Martin; Bonatto, Diego; Strauss, M.; Revers, L. F.; Pungartnik, Cristina; Saffi, Jenifer; Henriques, João Antônio Pêgas

doi:10.1016/j.mrrev.2003.06.018

Cited by 54 publications

(47 citation statements)

References 111 publications

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“…HPso4 is a human homolog of the PS04/PRP19 gene in S. cerevisiae that has pleiotropic functions in DNA recombination and errorprone repair (15,16,18,28,(33)(34)(35)(36)(37)(38). Specific role(s) for Pso4 in DSB repair is not known; however, it has been identified as a component of the nuclear matrix (20).…”

Section: Discussionmentioning

confidence: 99%

Human Pso4 Is a Metnase (SETMAR)-binding Partner That Regulates Metnase Function in DNA Repair

Beck

Park²,

Lee

et al. 2008

Journal of Biological Chemistry

138

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Metnase, also known as SETMAR, is a SET and transposase fusion protein with an undefined role in mammalian DNA repair. The SET domain is responsible for histone lysine methyltransferase activity at histone 3 K4 and K36, whereas the transposase domain possesses 5-terminal inverted repeat (TIR)-specific DNA binding, DNA looping, and DNA cleavage activities. Although the transposase domain is essential for Metnase function in DNA repair, it is not clear how a protein with sequencespecific DNA binding activity plays a role in DNA repair. Here, we show that human homolog of the ScPSO4/PRP19 (hPso4) forms a stable complex with Metnase on both TIR and non-TIR DNA. The transposase domain essential for Metnase-TIR interaction is not sufficient for its interaction with non-TIR DNA in the presence of hPso4. In vivo, hPso4 is induced and co-localized with Metnase following ionizing radiation treatment. Cells treated with hPso4-siRNA failed to show Metnase localization at DSB sites and Metnase-mediated stimulation of DNA end joining coupled to genomic integration, suggesting that hPso4 is necessary to bring Metnase to the DSB sites for its function(s) in DNA repair.Metnase (SETMAR) is a double strand break (DSB) 2 repair factor that contains two functional domains: a SET (Su(var)3-9, Enhancer-of-zeste, Trithorax) domain of histone lysine methyltransferase activity at histone 3, lysine 4, and lysine 36 (1) associated with chromatin opening (2-5) and a transposase domain containing the DDE motif (1, 6 -8), a conserved acidic motif essential for strand transfer and end joining activities among transposase and retroviral integrase families (9 -13). Deletion of either SET or transposase domain abolished Metnase function in vivo (1), suggesting that both domains are likely required for its role in DSB repair and genomic integration. Although Metnase is not an active transposase, it possesses most transposase functions such as sequence-specific DNA binding (6,11,14), assembly of paired end complexes (14), and DNA cleavage activity (11,14). Unlike other transposases, however, Metnase-mediated DNA cleavage was nonprocessive and occurred in the absence of the TIR sequence (11).Human Pso4 (hPso4) is a human homolog of the protein encoded by the PS04/PRP19 gene in Saccharomyces cerevisiae (15,16). PSO4 gene is essential for cell survival in yeast (15), and cells harboring a mutant Pso4 showed sensitivity to DNA crosslinking agents, suggesting that PSO4 is an essential DNA repair gene in S. cerevisiae (15). Pso4 is a part of the pre-mRNA splicing complex consisting of Pso4, Cdc5L, Plrg1, and Spf27 (17) and has been previously linked to DNA repair through a direct physical interaction between Cdc5L and WRN, the protein deficient in Werner syndrome (18). Human Pso4 contains six successive WD-40 motifs at the C terminus that is known to form a structural interface for the assembly of multiprotein complexes (19) and has been identified as a component of the nuclear matrix (20). Pso4 is also a U-box protein with associated E3 ubiquitin ligase...

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Section: Discussionmentioning

confidence: 99%

Human Pso4 Is a Metnase (SETMAR)-binding Partner That Regulates Metnase Function in DNA Repair

Beck

Park²,

Lee

et al. 2008

Journal of Biological Chemistry

138

View full text Add to dashboard Cite

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“…Thus, Aquarius is a key factor linking the biogenesis of small nucleolar ribonucleoprotein to pre-mRNA splicing (33,34). PRP19 is a spliceosome-associated protein and plays an essential role in pre-mRNA splicing (35)(36)(37). hPRP19 has been purified as a stable protein complex consisting of hCDC5, XAB2, hAquarius (IBP160), hISY1, PPIE, and additional proteins in the activated spliceosome (36,38).…”

Section: Discussionmentioning

confidence: 99%

“…The hPRP19 complex itself is part of a large ribonucleoprotein complex containing U2, U5, and U6 small nuclear RNA (snRNA), and is required prior to the first and/or second catalytic step(s) of pre-mRNA splicing. On the other hand, PRP19 is allelic to PSO4, which is known to be involved in the repair of DNA cross-linking damage (35,37,39). ISY1 associates with SYF1 (yeast XAB2) and snRNAs (U5 and U6 snRNAs) which are part of the spliceosome (29,30,40), and it is required for the optimization of pre-mRNA splicing (30) and cell cycle arrest through activation of the spindle checkpoint (29).…”

Section: Discussionmentioning

confidence: 99%

Isolation of XAB2 Complex Involved in Pre-mRNA Splicing, Transcription, and Transcription-coupled Repair

Kuraoka

Ito

Wada

et al. 2008

Journal of Biological Chemistry

112

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Nucleotide excision repair is a versatile repair pathway that counteracts the deleterious effects of various DNA lesions. In nucleotide excision repair, there is a transcription-coupled repair (TCR) pathway that focuses on DNA damage that blocks RNA polymerase IIo in transcription elongation. XAB2 (XPAbinding protein 2), containing tetratricopeptide repeats, has been isolated by virtue of its ability to interact with xeroderma pigmentosum group A protein (XPA). Moreover, XAB2 has been shown to interact with Cockayne syndrome group A and B proteins (CSA and CSB) and RNA polymerase II, as well as XPA, and is involved in TCR and transcription. Here we purified XAB2 as a multimeric protein complex consisting of hAquarius, XAB2, hPRP19, CCDC16, hISY1, and PPIE, which are involved in pre-mRNA splicing. Knockdown of XAB2 with small interfering RNA in HeLa cells resulted in a hypersensitivity to killing by UV light and a decreased recovery of RNA synthesis after UV irradiation and regular RNA synthesis. Enhanced interaction of XAB2 with RNA polymerase IIo or XPA was observed in cells treated with DNA-damaging agents, indicating DNA damageresponsive activity of the XAB2 complex. These results indicated that the XAB2 complex is a multifunctional factor involved in pre-mRNA splicing, transcription, and TCR.

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“…In the yeast Saccharomyces cerevisiae, three distinct pathways, including nucleotide excision repair (NER), homologous recombination (HR), and translesion synthesis (TLS), participate in ICL repair (7,20). In addition, yeast SNM1 (also known as PSO2) specifically functions in ICL repair without apparently participating directly in any of these pathways (2,9). During the repair process, NER mediates incisions on both sides of the cross-linked DNA (sometimes termed "unhooking") (5), and double-strand breaks (DSBs), which are probably associated with the collapse of a replication fork, are formed.…”

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confidence: 99%

DNA Cross-Link Repair Protein SNM1A Interacts with PIAS1 in Nuclear Focus Formation

Ishiai

Kimura

Namikoshi

et al. 2004

Molecular and Cellular Biology

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The yeast SNM1/PSO2 gene specifically functions in DNA interstrand cross-link (ICL) repair, and its role has been suggested to be separate from other DNA repair pathways. In vertebrates, there are three homologs of SNM1 (SNM1A, SNM1B, and SNM1C/Artemis; SNM1 family proteins) whose functions are largely unknown. We disrupted each of the SNM1 family genes in the chicken B-cell line DT40. Both SNM1A-and SNM1B-deficient cells were sensitive to cisplatin but not to X-rays, whereas SNM1C/Artemis-deficient cells exhibited sensitivity to X-rays but not to cisplatin. SNM1A was nonepistatic with XRCC3 (homologous recombination), RAD18 (translesion synthesis), FANCC (Fanconi anemia), and SNM1B in ICL repair. SNM1A protein formed punctate nuclear foci depending on the conserved SNM1 (metallo-␤-lactamase) domain. PIAS1 was found to physically interact with SNM1A, and they colocalized at nuclear foci. Point mutations in the SNM1 domain, which disrupted the interaction with PIAS1, led to mislocalization of SNM1A in the nucleus and loss of complementation of snm1a cells. These results suggest that interaction between SNM1A and PIAS1 is required for ICL repair.DNA interstrand cross-links (ICLs) covalently bind the two complementary strands of the double helix of DNA. They severely impair fundamental processes of DNA metabolism such as transcription or replication, leading to cell death if they are left unrepaired. Current protocols for cancer chemotherapy often include ICL-inducing agents, i.e., mitomycin C (MMC) or cisplatin, for effective killing of malignant cells (reviewed in references 7 and 21).The molecular mechanism of ICL repair is still poorly understood. In the yeast Saccharomyces cerevisiae, three distinct pathways, including nucleotide excision repair (NER), homologous recombination (HR), and translesion synthesis (TLS), participate in ICL repair (7,20). In addition, yeast SNM1 (also known as PSO2) specifically functions in ICL repair without apparently participating directly in any of these pathways (2, 9). During the repair process, NER mediates incisions on both sides of the cross-linked DNA (sometimes termed "unhooking") (5), and double-strand breaks (DSBs), which are probably associated with the collapse of a replication fork, are formed. The DSBs are then repaired by HR mechanisms. The interdependence between unhooking and formation of DSBs remains unclear (7). Yeast snm1 mutants are proficient in unhooking but are unable to process DSB intermediates (7,19,40).In mammalian cells, the situation is even more complex.Among NER factors, XPF/ERCC1 endonuclease appears to be particularly important for the unhooking of ICLs (5,21,26,32). Hamster mutant cells lacking the RAD51 paralog XRCC2 or XRCC3 display extreme sensitivity to ICLs, indicating an important role of HR in mammalian ICL repair (17). Cells from Fanconi anemia (FA) patients are also highly sensitive to ICL reagents (33), but the role of FA proteins in ICL repair is still unclear (4). Furthermore, there are three homologs of SNM1 (referred to as SNM1A, S...

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Role of PSO genes in repair of DNA damage of Saccharomyces cerevisiae

Cited by 54 publications

References 111 publications

Human Pso4 Is a Metnase (SETMAR)-binding Partner That Regulates Metnase Function in DNA Repair

Human Pso4 Is a Metnase (SETMAR)-binding Partner That Regulates Metnase Function in DNA Repair

Isolation of XAB2 Complex Involved in Pre-mRNA Splicing, Transcription, and Transcription-coupled Repair

DNA Cross-Link Repair Protein SNM1A Interacts with PIAS1 in Nuclear Focus Formation

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