Pol32, an accessory subunit of DNA polymerase delta, plays an essential role in genome stability and pathogenesis of Candida albicans

References

• Burgers PMJ, Kunkel TA. Eukaryotic DNA replication fork. Annu Rev Biochem. 2017;86(1):417–35. doi:10.1146/annurev-biochem-061516-044709.
   PubMedGoogle Scholar
• Guilliam TA, Yeeles JTP. An updated perspective on the polymerase division of labor during eukaryotic DNA replication. Crit Rev Biochem Mol Biol. 2020;55(5):469–481. doi:10.1080/10409238.2020.1811630.
   PubMed Web of Science ®Google Scholar
• Acharya N, Klassen R, Johnson RE, Prakash L, Prakash S. 2011. PCNA binding domains in all three subunits of yeast DNA polymerase delta modulate its function in DNA replication. Proceedings of the National Academy of Sciences of the United States of America; 108, 17927–17932. doi:10.1073/pnas.1109981108.
   Google Scholar
• Acharya N, Khandagale P, Thakur S, Sahu JK, Utkalaja BG. Quaternary structural diversity in eukaryotic DNA polymerases: monomeric to multimeric form. Curr Genet. 2020;66(4):635–655. doi:10.1007/s00294-020-01071-1.
   PubMed Web of Science ®Google Scholar
• Khandagale P, Peroumal D, Manohar K, Acharya N. Human DNA polymerase delta is a pentameric holoenzyme with a dimeric p12 subunit. Life Sci Alliance. 2019;2(2):e201900323. doi:10.26508/lsa.201900323.
   PubMed Web of Science ®Google Scholar
• Zuo S, Gibbs E, Kelman Z, Wang TS, O’Donnell M, MacNeill SA, Hurwitz J. (1997). DNA polymerase delta isolated from Schizosaccharomyces pombe contains five subunits. Proceedings of the National Academy of Sciences of the United States of America; 94, 11244–11249. doi:10.1073/pnas.94.21.11244.
   Google Scholar
• Johansson E, Garg P, Burgers PM. The Pol32 subunit of DNA polymerase delta contains separable domains for processive replication and proliferating cell nuclear antigen (PCNA) binding. J Biol Chem. 2004;279(3):1907–1915. doi:10.1074/jbc.M310362200.
   PubMed Web of Science ®Google Scholar
• MacNeill SA, Moreno S, Reynolds N, Nurse P, Fantes PA. The fission yeast Cdc1 protein, a homologue of the small subunit of DNA polymerase delta, binds to Pol3 and Cdc27. EMBO J. 1996;15(17):4613–4628. doi:10.1002/j.1460-2075.1996.tb00839.x.
   PubMed Web of Science ®Google Scholar
• Makarova AV, Stodola JL, Burgers PM. A four-subunit DNA polymerase zeta complex containing Pol delta accessory subunits is essential for PCNA-mediated mutagenesis. Nucleic Acids Res. 2012;40(22):11618–11626. doi:10.1093/nar/gks948.
   PubMed Web of Science ®Google Scholar
• Johnson RE, Prakash L, Prakash S. 2012. Pol31 and Pol32 subunits of yeast DNA polymerase delta are also essential subunits of DNA polymerase zeta. Proceedings of the National Academy of Sciences of the United States of America; 109, 12455–12460. doi:10.1073/pnas.1206052109.
   Google Scholar
• Huang ME, Rio AG, Galibert MD, Galibert F. Pol32, a subunit of Saccharomyces cerevisiae DNA polymerase δ, suppresses genomic deletions and is involved in the mutagenic bypass pathway. Genetics. 2002;160(4):1409–1422. doi:10.1093/genetics/160.4.1409.
   PubMed Web of Science ®Google Scholar
• Acharya N, Johnson RE, Pages V, Prakash L, Prakash S. 2009. Yeast Rev1 protein promotes complex formation of DNA polymerase zeta with Pol32 subunit of DNA polymerase delta. Proceedings of the National Academy of Sciences of the United States of America; 106, 9631–9636
   Google Scholar
• Hirota K, Yoshikiyo K, Guilbaud G, Tsurimoto T, Murai J, Tsuda M, Phillips LG, Narita T, Nishihara K, Kobayashi K, et al. The POLD3 subunit of DNA polymerase delta can promote translesion synthesis independently of DNA polymerase zeta. Nucleic Acids Res. 2015;43(3):1671–1683. doi:10.1093/nar/gkv023.
   PubMed Web of Science ®Google Scholar
• Lancey C, Tehseen M, Raducanu VS, Rashid F, Merino N, Ragan TJ, Savva CG, Zaher MS, Shirbini A, Blanco FJ, et al. Structure of the processive human Pol delta holoenzyme. Nat Commun. 2020;11(1):1109. doi:10.1038/s41467-020-14898-6.
   PubMed Web of Science ®Google Scholar
• Zheng F, Georgescu RE, Li H, O’Donnell ME. 2020. Structure of eukaryotic DNA polymerase delta bound to the PCNA clamp while encircling DNA. Proceedings of the National Academy of Sciences of the United States of America; 117, 30344–30353. doi:10.1073/pnas.2017637117.
   Google Scholar
• Wenzel RP. Nosocomial candidemia: risk factors and attributable mortality. Clin Infect Dis. 1995;20(6):1531–1534. doi:10.1093/clinids/20.6.1531.
   PubMed Web of Science ®Google Scholar
• Sahu SR, Bose S, Singh M, Kumari P, Dutta A, Utkalaja BG, Patel SK, Acharya N. Vaccines against candidiasis: status, challenges and emerging opportunity. Front Cell Infect Microbiol. 2022;12:1002406. doi:10.3389/fcimb.2022.1002406.
   PubMed Web of Science ®Google Scholar
• Hirakawa MP, Martinez DA, Sakthikumar S, Anderson MZ, Berlin A, Gujja S, Zeng Q, Zisson E, Wang JM, Greenberg JM, et al. Genetic and phenotypic intra-species variation in Candida albicans. Genome Res. 2015;25(3):413–425. doi:10.1101/gr.174623.114.
   PubMed Web of Science ®Google Scholar
• Pavlov YI, Zhuk AS, Stepchenkova EI. DNA polymerases at the eukaryotic replication fork thirty years after: connection to cancer. Cancers (Basel). 2020;12(12):3489. doi:10.3390/cancers12123489.
   PubMed Web of Science ®Google Scholar
• Rustchenko E. Chromosome instability in Candida albicans. FEMS Yeast Res. 2007;7(1):2–11. doi:10.1111/j.1567-1364.2006.00150.x.
   PubMed Web of Science ®Google Scholar
• Kumari P, Sundaram R, Manohar K, Vasudevan D, Acharya N. Interdomain connecting loop and J loop structures determine cross-species compatibility of PCNA. J Biol Chem. 2021;297(1):100911. doi:10.1016/j.jbc.2021.100911.
   PubMed Web of Science ®Google Scholar
• Huang ME, Le Douarin B, Henry C, Galibert F. The Saccharomyces cerevisiae protein YJR043C (Pol32) interacts with the catalytic subunit of DNA polymerase alpha and is required for cell cycle progression in G2/M. Mol Gen Genet. 1999;260(6):541–550. doi:10.1007/s004380050927.
   PubMedGoogle Scholar
• Manohar K, Peroumal D, Acharya N. TLS dependent and independent functions of DNA polymerase eta (Polη/Rad30) from pathogenic yeast Candida albicans. Mol Microbiol. 2018;110(5):707–727. doi:10.1111/mmi.14004.
   PubMed Web of Science ®Google Scholar
• Forche A, Abbey D, Pisithkul T, Weinzierl MA, Ringstrom T, Bruck D, Petersen K, Berman J. Stress alters rates and types of loss of heterozygosity in Candida albicans. mBio. 2011;2. doi:10.1128/mBio.00129-11.
   PubMed Web of Science ®Google Scholar
• Ene IV, Farrer RA, Hirakawa MP, Agwamba K, Cuomo CA, Bennett RJ. 2018. Global analysis of mutations driving microevolution of a heterozygous diploid fungal pathogen. Proceedings of the National Academy of Sciences of the United States of America; 115, E8688–E8697. doi:10.1073/pnas.1806002115.
   Google Scholar
• Ford CB, Funt JM, Abbey D, Issi L, Guiducci C, Martinez DA, Delorey T, Li BY, White TC, Cuomo C, et al. The evolution of drug resistance in clinical isolates of Candida albicans. eLife. 2015;4:e00662. doi:10.7554/eLife.00662.
   PubMed Web of Science ®Google Scholar
• Abbey DA, Funt J, Lurie-Weinberger MN, Thompson DA, Regev A, Myers CL, Berman J. YMAP: a pipeline for visualization of copy number variation and loss of heterozygosity in eukaryotic pathogens. Genome Med. 2014;6(11):100. doi:10.1186/s13073-014-0100-8.
   PubMedGoogle Scholar
• Nick Mcelhinny SA, Stith CM, Burgers PM, Kunkel TA. Inefficient proofreading and biased error rates during inaccurate DNA synthesis by a mutant derivative of Saccharomyces cerevisiae DNA polymerase delta. J Biol Chem. 2007;282(4):2324–2332. doi:10.1074/jbc.M609591200.
   PubMed Web of Science ®Google Scholar
• Lujan SA, Clausen AR, Clark AB, MacAlpine HK, MacAlpine DM, Malc EP, Mieczkowski PA, Burkholder AB, Fargo DC, Gordenin DA, et al. Heterogeneous polymerase fidelity and mismatch repair bias genome variation and composition. Genome Res. 2014;24(11):1751–1764. doi:10.1101/gr.178335.114.
   PubMed Web of Science ®Google Scholar
• Bachewich C, Thomas DY, Whiteway M. Depletion of a polo-like kinase in candida albicans activates cyclase-dependent hyphal-like growth. Mol Biol Cell. 2003;14(5):2163–2180. doi:10.1091/mbc.02-05-0076.
   PubMed Web of Science ®Google Scholar
• Shi QM, Wang YM, Zheng XD, Lee RT, Wang Y. Critical role of DNA checkpoints in mediating genotoxic-stress–induced filamentous growth in Candida albicans. Mol Biol Cell. 2007;18(3):815–826. doi:10.1091/mbc.e06-05-0442.
   PubMed Web of Science ®Google Scholar
• Loll-Krippleber R, d’Enfert C, Feri A, Diogo D, Perin A, Marcet-Houben M, Bougnoux ME, Legrand M. A study of the DNA damage checkpoint in Candida albicans: uncoupling of the functions of Rad53 in DNA repair, cell cycle regulation and genotoxic stress-induced polarized growth. Mol Microbiol. 2014;91(3):452–471. doi:10.1111/mmi.12471.
   PubMed Web of Science ®Google Scholar
• Peroumal D, Manohar K, Patel SK, Kumari P, Sahu SR, Acharya N. Virulence and pathogenicity of a Candida albicans mutant with reduced filamentation. Cell Microbiol. 2019;21(12):e13103. doi:10.1111/cmi.13103.
   PubMed Web of Science ®Google Scholar
• Tsuchimori N, Sharkey LL, Fonzi WA, French SW, Edwards JE Jr., Filler SG. Reduced virulence of HWP1 -deficient mutants of Candida albicans and their interactions with host cells. Infect Immun. 2000;68(4):1997–2002. doi:10.1128/IAI.68.4.1997-2002.2000.
   PubMed Web of Science ®Google Scholar
• Correia A, Lermann U, Teixeira L, Cerca F, Botelho S, da Costa RM, Sampaio P, Gartner F, Morschhauser J, Vilanova M, et al. Limited role of secreted aspartyl proteinases sap1 to sap6 in Candida albicans virulence and host immune response in murine hematogenously disseminated candidiasis. Infect Immun. 2010;78(11):4839–4849. doi:10.1128/IAI.00248-10.
   PubMed Web of Science ®Google Scholar
• Lo HJ, Kohler JR, DiDomenico B, Loebenberg D, Cacciapuoti A, Fink GR. Nonfilamentous C. albicans mutants are avirulent. Cell. 1997;90(5):939–949. doi:10.1016/S0092-8674(00)80358-X.
   PubMed Web of Science ®Google Scholar
• Murad AM, Leng P, Straffon M, Wishart J, Macaskill S, MacCallum D, Schnell N, Talibi D, Marechal D, Tekaia F, et al. NRG1 represses yeast-hypha morphogenesis and hypha-specific gene expression in Candida albicans. EMBO J. 2001;20(17):4742–4752. doi:10.1093/emboj/20.17.4742.
   PubMed Web of Science ®Google Scholar
• Moyes DL, Wilson D, Richardson JP, Mogavero S, Tang SX, Wernecke J, Hofs S, Gratacap RL, Robbins J, Runglall M, et al. Candidalysin is a fungal peptide toxin critical for mucosal infection. Nature. 2016;532(7597):64–68. doi:10.1038/nature17625.
   PubMed Web of Science ®Google Scholar
• Cowen LE, Anderson JB, Kohn LM. Evolution of drug resistance in Candida Albicans. Annu Rev Microbiol. 2002;56(1):139–165. doi:10.1146/annurev.micro.56.012302.160907.
   PubMedGoogle Scholar
• Marie C, White TC. Genetic basis of antifungal drug resistance. Curr Fungal Infect Rep. 2009;3(3):163–169. doi:10.1007/s12281-009-0021-y.
   PubMedGoogle Scholar
• Dunkel N, Blass J, Rogers PD, Morschhauser J. Mutations in the multi-drug resistance regulator MRR1, followed by loss of heterozygosity, are the main cause of MDR1 overexpression in fluconazole-resistant Candida albicans strains. Mol Microbiol. 2008;69(4):827–840. doi:10.1111/j.1365-2958.2008.06309.x.
   PubMed Web of Science ®Google Scholar
• Robbins N, Uppuluri P, Nett J, Rajendran R, Ramage G, Lopez-Ribot JL, Andes D, Cowen LE. Hsp90 governs dispersion and drug resistance of fungal biofilms. PLoS Pathog. 2011;7(9):e1002257. doi:10.1371/journal.ppat.1002257.
   PubMed Web of Science ®Google Scholar
• LaFayette SL, Collins C, Zaas AK, Schell WA, Betancourt-Quiroz M, Gunatilaka AA, Perfect JR, Cowen LE. PKC signaling regulates drug resistance of the fungal pathogen Candida albicans via circuitry comprised of Mkc1, calcineurin, and Hsp90. PLoS Pathog. 2010;6(8):e1001069. doi:10.1371/journal.ppat.1001069.
   PubMed Web of Science ®Google Scholar
• Regan J, DeJarnette C, Luna-Tapia A, Parker JE, Reitler P, Barnett S, Tucker KM, Kelly SL, Palmer GE. Titration of C-5 sterol desaturase activity reveals its relationship to Candida albicans virulence and antifungal susceptibility is dependent upon host immune status. mBio. 2022;13(2):e0011522. doi:10.1128/mbio.00115-22.
   PubMed Web of Science ®Google Scholar
• Robbins N, Caplan T, Cowen LE. Molecular evolution of antifungal drug resistance. Annu Rev Microbiol. 2017;71(1):753–775. doi:10.1146/annurev-micro-030117-020345.
   PubMedGoogle Scholar
• Shapiro RS, Uppuluri P, Zaas AK, Collins C, Senn H, Perfect JR, Heitman J, Cowen LE. Hsp90 orchestrates temperature-dependent Candida albicans morphogenesis via Ras1-PKA signaling. Curr Biol. 2009;19(8):621–629. doi:10.1016/j.cub.2009.03.017.
   PubMed Web of Science ®Google Scholar
• Cowen LE, Singh SD, Kohler JR, Collins C, Zaas AK, Schell WA, Aziz H, Mylonakis E, Perfect JR, Whitesell L, et al. 2009. Harnessing Hsp90 function as a powerful, broadly effective therapeutic strategy for fungal infectious disease. Proceedings of the National Academy of Sciences of the United States of America; 106, 2818–2823. doi:10.1073/pnas.0813394106.
   Google Scholar
• Li Y, Chang W, Zhang M, Li X, Jiao Y, Lou H. Synergistic and drug-resistant reversing effects of diorcinol D combined with fluconazole against Candida albicans. FEMS Yeast Res. 2015;15(2). doi:10.1093/femsyr/fov001.
   Web of Science ®Google Scholar
• Garcia-Rubio R, de Oliveira HC, Rivera J, Trevijano-Contador N. The fungal cell wall: candida, cryptococcus, and aspergillus species. Front Microbiol. 2019;10:2993. doi:10.3389/fmicb.2019.02993.
   PubMed Web of Science ®Google Scholar
• Desai JV, Mitchell AP. Candida albicans biofilm development and its genetic control. Microbiol Spectr. 2015;3(3). doi:10.1128/microbiolspec.MB-0005-2014.
   PubMedGoogle Scholar
• Finkel JS, Mitchell AP. Genetic control of Candida albicans biofilm development. Nat Rev Microbiol. 2011;9(2):109–118. doi:10.1038/nrmicro2475.
   PubMed Web of Science ®Google Scholar
• Gulati M, Nobile CJ. Candida albicans biofilms: development, regulation, and molecular mechanisms. Microbes Infect /Institut Pasteur. 2016;18(5):310–321. doi:10.1016/j.micinf.2016.01.002.
   PubMed Web of Science ®Google Scholar
• Jain R, Rice WJ, Malik R, Johnson RE, Prakash L, Prakash S, Ubarretxena-Belandia I, Aggarwal AK. Cryo-EM structure and dynamics of eukaryotic DNA polymerase delta holoenzyme. Nat Struct Mol Biol. 2019;26(10):955–962. doi:10.1038/s41594-019-0305-z.
   PubMed Web of Science ®Google Scholar
• Gerik KJ, Li X, Pautz A, Burgers PM. Characterization of the two small subunits of Saccharomyces cerevisiae DNA polymerase delta. J Biol Chem. 1998;273(31):19747–19755. doi:10.1074/jbc.273.31.19747.
   PubMed Web of Science ®Google Scholar
• Reijns MAM, Kemp H, Ding J, de Proce SM, Jackson AP, Taylor MS. Lagging-strand replication shapes the mutational landscape of the genome. Nature. 2015;518(7540):502–506. doi:10.1038/nature14183.
   PubMed Web of Science ®Google Scholar
• Torres EM, Williams BR, Amon A. Aneuploidy: cells losing their balance. Genetics. 2008;179(2):737–746. doi:10.1534/genetics.108.090878.
   PubMed Web of Science ®Google Scholar
• Pavelka N, Rancati G, Zhu J, Bradford WD, Saraf A, Florens L, Sanderson BW, Hattem GL, Li R. Aneuploidy confers quantitative proteome changes and phenotypic variation in budding yeast. Nature. 2010;468(7321):321–325. doi:10.1038/nature09529.
   PubMed Web of Science ®Google Scholar
• Khristich AN, Armenia JF, Matera RM, Kolchinski AA, Mirkin SM. 2020. Large-scale contractions of Friedreich’s ataxia GAA repeats in yeast occur during DNA replication due to their triplex-forming ability. Proceedings of the National Academy of Sciences of the United States of America; 117, 1628–1637. doi:10.1073/pnas.1913416117.
   Google Scholar
• Braun BR, Kadosh D, Johnson AD. NRG1, a repressor of filamentous growth in C.albicans, is down-regulated during filament induction. EMBO J. 2001;20(17):4753–4761. doi:10.1093/emboj/20.17.4753.
   PubMed Web of Science ®Google Scholar
• Sanglard D, Ischer F, Parkinson T, Falconer D, Bille J. Candida albicans mutations in the ergosterol biosynthetic pathway and resistance to several antifungal agents. Antimicrob Agents Chemother. 2003;47(8):2404–2412. doi:10.1128/AAC.47.8.2404-2412.2003.
   PubMed Web of Science ®Google Scholar
• Belenky P, Camacho D, Collins JJ. Fungicidal drugs induce a common oxidative-damage cellular death pathway. Cell Rep. 2013;3(2):350–358. doi:10.1016/j.celrep.2012.12.021.
   PubMed Web of Science ®Google Scholar
• Sottile ML, Nadin SB. Heat shock proteins and DNA repair mechanisms: an updated overview. Cell Stress Chaperones. 2018;23(3):303–315. doi:10.1007/s12192-017-0843-4.
   PubMed Web of Science ®Google Scholar
• Robbins N, Leach MD, Cowen LE. Lysine deacetylases Hda1 and Rpd3 regulate Hsp90 function thereby governing fungal drug resistance. Cell Rep. 2012;2(4):878–888. doi:10.1016/j.celrep.2012.08.035.
   PubMed Web of Science ®Google Scholar
• Saville SP, Lazzell AL, Chaturvedi AK, Monteagudo C, Lopez-Ribot JL. Efficacy of a genetically engineered Candida albicans tet-NRG1 strain as an experimental live attenuated vaccine against hematogenously disseminated candidiasis. Clin Vaccine Immunol. 2009;16(3):430–432. doi:10.1128/CVI.00480-08.
   PubMed Web of Science ®Google Scholar
• Hube B, Sanglard D, Odds FC, Hess D, Monod M, Schafer W, Brown AJ, Gow NA. Disruption of each of the secreted aspartyl proteinase genes SAP1, SAP2, and SAP3 of Candida albicans attenuates virulence. Infect Immun. 1997;65(9):3529–3538. doi:10.1128/iai.65.9.3529-3538.1997.
   PubMed Web of Science ®Google Scholar
• Acharya N, Haracska L, Johnson RE, Unk I, Prakash S, Prakash L. Complex formation of yeast Rev1 and Rev7 proteins: a novel role for the polymerase-associated domain. Mol Cell Biol. 2005;25(21):9734–9740. doi:10.1128/MCB.25.21.9734-9740.2005.
   PubMed Web of Science ®Google Scholar
• Manohar K, Acharya N. Characterization of proliferating cell nuclear antigen (PCNA) from pathogenic yeast Candida albicans and its functional analyses in S. cerevisiae. BMC Microbiol. 2015;15(1):257. doi:10.1186/s12866-015-0582-6.
   PubMedGoogle Scholar
• Manohar K, Khandagale P, Patel SK, Sahu JK, Acharya N. The ubiquitin-binding domain of DNA polymerase eta directly binds to DNA clamp PCNA and regulates translesion DNA synthesis. J Biol Chem. 2022;298(2):101506. doi:10.1016/j.jbc.2021.101506.
   PubMed Web of Science ®Google Scholar
• Sasse C, Morschhauser J. Gene deletion in Candida albicans wild-type strains using the SAT1-flipping strategy. Methods Mol Biol. 2012;845:3–17.
   PubMedGoogle Scholar
• Oliveira Carvalho V, Okay TS, Melhem MS, Walderez Szeszs M, Del Negro GM. The new mutation L321F in Candida albicans ERG11 gene may be associated with fluconazole resistance. Rev Iberoam Micol. 2013;30(3):209–212. doi:10.1016/j.riam.2013.01.001.
   PubMed Web of Science ®Google Scholar
• Khandelwal NK, Chauhan N, Sarkar P, Esquivel BD, Coccetti P, Singh A, Coste AT, Gupta M, Sanglard D, White TC, et al. Azole resistance in a Candida albicans mutant lacking the ABC transporter CDR6/ROA1 depends on TOR signaling. J Biol Chem. 2018;293(2):412–432. doi:10.1074/jbc.M117.807032.
   PubMed Web of Science ®Google Scholar
• Grigor’eva A, Bardasheva A, Tupitsyna A, Amirkhanov N, Tikunova N, Pyshnyi D, Kleshev M, Ryabchikova E. Changes in the ultrastructure of candida albicans treated with cationic peptides. Microorganisms. 2020;8. doi:10.3390/microorganisms8040582.
   Web of Science ®Google Scholar
• Suwunnakorn S, Wakabayashi H, Rustchenko E. Chromosome 5 of human pathogen Candida albicans carries multiple genes for negative control of caspofungin and anidulafungin susceptibility. Antimicrob Agents Chemother. 2016;60(12):7457–7467. doi:10.1128/AAC.01888-16.
   PubMed Web of Science ®Google Scholar