Radiation Oncology

Marc S. Wold, PhD

Portrait

Professor of Biochemistry
Professor of Radiation Oncology

Contact Information

Primary Office: 3107 MERF
Iowa City, IA 52242
Primary Office Phone: 319-335-6784

Email: marc-wold@uiowa.edu
Web: Wold Laboratory

Education


BS, Chemistry, California Institute of Technology
PhD, Biochemistry, The Johns Hopkins University

Post Doctoral, Molecular Biology & Genetics, The Johns Hopkins University

Education/Training Program Affiliations

Biosciences Graduate Program
Department of Biochemistry PhD
Free Radical and Radiation Biology Graduate Program
Interdisciplinary Graduate Program in Molecular and Cellular Biology
Interdisciplinary Graduate Program in Translational Biomedicine
Medical Scientist Training Program

Research Summary

The human genome is composed of ~4x109 base pairs of DNA. In order to grow, a human cell must precisely duplicate this entire genome each cell cycle and continuously protect it from damage or modification. Defects in DNA replication or repair result in higher rates of mutation, chromosome instability and have a direct role in a number of human diseases such as contributing to the development of cancer or causing genetic diseases such as Fragile X and Xeroderma Pigmentosum. Replication protein A (RPA) is a multi-functional, single-stranded DNA-binding protein. RPA is essential for DNA replication, DNA repair, recombination and coordination of the cellular response to DNA damage. RPA is composed of six structurally conserved DNA binding domains that are distributed in three subunits. The functions of these domains are poorly understood. RPA is also phosphorylated during S-phase and in response to DNA damage. Recent studies have shown that RPA hyper-phosphorylation modulates RPA activity and plays a role in the cellular response to DNA damage; however, the mechanism of this regulation is also poorly understood. Our current research focuses on utilizing a combination of in vitro and in vivo approaches to define functions of the domains of RPA and understanding the role of RPA in regulating cellular DNA metabolism. We are using molecular approaches to generate specific mutant forms of RPA. Biochemical and structural analyses are used to define the interactions of RPA with the different DNA substrates and protein complexes. We have also have recently established a system that uses RNAi and plasmid directed expression of exogenous genes to examine the activity of wild-type and mutant RPA genes in human cells. These studies will lead to a better understanding of the molecular mechanisms of cellular DNA metabolism and will contribute to developing new treatments for diseases associated with defects in DNA repair or replication.

Center, Program and Institute Affiliations

Holden Comprehensive Cancer Center

All Publications

Sparks J, Kumar R, Singh M, Wold M, Pandita T, Burgers P.  Human exonuclease 5 is a novel sliding exonuclease required for genome stability.  The Journal of biological chemistry.  2012 December. 287(51):42773-83.
[PubMed]

Lindsey-Boltz L, Reardon J, Wold M, Sancar A.  In vitro analysis of the role of replication protein A (RPA) and RPA phosphorylation in ATR-mediated checkpoint signaling.  The Journal of biological chemistry.  2012 October. 287(43):36123-31.
[PubMed]

Hass C, Lam K, Wold M.  Repair-specific functions of replication protein A.  The Journal of biological chemistry.  2012 February. 287(6):3908-18.
[PubMed]

Hass C, Chen R, Wold M.  Detection of posttranslational modifications of replication protein A.  Methods in molecular biology (Clifton, N.J.).  2012. 922:193-204.
[PubMed]

Neal J, Dang V, Douglas P, Wold M, Lees-Miller S, Meek K.  Inhibition of homologous recombination by DNA-dependent protein kinase requires kinase activity, is titratable, and is modulated by autophosphorylation.  Molecular and cellular biology.  2011 April. 31(8):1719-33.
[PubMed]

Machwe A, Lozada E, Wold M, Li G, Orren D.  Molecular cooperation between the Werner syndrome protein and replication protein A in relation to replication fork blockage.  The Journal of biological chemistry.  2011 February. 286(5):3497-508.
[PubMed]

Choi J, Lindsey-Boltz L, Kemp M, Mason A, Wold M, Sancar A.  Reconstitution of RPA-covered single-stranded DNA-activated ATR-Chk1 signaling.  Proceedings of the National Academy of Sciences of the United States of America.  2010 August. 107(31):13660-5.
[PubMed]

Hass C, Gakhar L, Wold M.  Functional characterization of a cancer causing mutation in human replication protein A.  Molecular cancer research : MCR.  2010 July. 8(7):1017-26.
[PubMed]

Mason A, Roy R, Simmons D, Wold M.  Functions of alternative replication protein A in initiation and elongation.  Biochemistry.  2010 July. 49(28):5919-28.
[PubMed]

Kemp M, Mason A, Carreira A, Reardon J, Haring S, Borgstahl G, Kowalczykowski S, Sancar A, Wold M.  An alternative form of replication protein a expressed in normal human tissues supports DNA repair.  The Journal of biological chemistry.  2010 February. 285(7):4788-97.
[PubMed]

Humphreys T, Wold M.  Eukaryotic replication protein A.  Encyclopedia of Life Science, John Wiley & Sons, Ltd. Chichester;  2010. 

Haring S, Humphreys T, Wold M.  A naturally occurring human RPA subunit homolog does not support DNA replication or cell-cycle progression.  Nucleic acids research.  2010 January. 38(3):846-58.
[PubMed]

Suhasini A, Sommers J, Mason A, Voloshin O, Camerini-Otero R, Wold M, Brosh R.  FANCJ helicase uniquely senses oxidative base damage in either strand of duplex DNA and is stimulated by replication protein A to unwind the damaged DNA substrate in a strand-specific manner.  The Journal of biological chemistry.  2009 July. 284(27):18458-70.
[PubMed]

Dickson A, Krasikova Y, Pestryakov P, Lavrik O, Wold M.  Essential functions of the 32 kDa subunit of yeast replication protein A.  Nucleic acids research.  2009 April. 37(7):2313-26.
[PubMed]

Mason A, Haring S, Pryor J, Staloch C, Gan T, Wold M.  An alternative form of replication protein a prevents viral replication in vitro.  The Journal of biological chemistry.  2009 February. 284(8):5324-31.
[PubMed]

Bartos J, Willmott L, Binz S, Wold M, Bambara R.  Catalysis of strand annealing by replication protein A derives from its strand melting properties.  The Journal of biological chemistry.  2008 August. 283(31):21758-68.
[PubMed]

Binz S, Wold M.  Regulatory functions of the N-terminal domain of the 70-kDa subunit of replication protein A (RPA).  The Journal of biological chemistry.  2008 August. 283(31):21559-70.
[PubMed]

Haring S, Mason A, Binz S, Wold M.  Cellular functions of human RPA1. Multiple roles of domains in replication, repair, and checkpoints.  The Journal of biological chemistry.  2008 July. 283(27):19095-111.
[PubMed]

Kuhn-Parnell E, Helou C, Marion D, Gilmore B, Parnell T, Wold M, Geyer P.  Investigation of the properties of non-gypsy suppressor of hairy-wing-binding sites.  Genetics.  2008 July. 179(3):1263-73.
[PubMed]

Deng X, Habel J, Kabaleeswaran V, Snell E, Wold M, Borgstahl G.  Structure of the full-length human RPA14/32 complex gives insights into the mechanism of DNA binding and complex formation.  Journal of molecular biology.  2007 December. 374(4):865-76.
[PubMed]

Haring S, Wold M.  A common means to an end.  Nature structural & molecular biology.  2007 March. 14(3):176-7.
[PubMed]

Grudic A, Jul-Larsen A, Haring S, Wold M, Lønning P, Bjerkvig R, Bøe S.  Replication protein A prevents accumulation of single-stranded telomeric DNA in cells that use alternative lengthening of telomeres.  Nucleic acids research.  2007. 35(21):7267-78.
[PubMed]

Majka J, Binz S, Wold M, Burgers P.  Replication protein A directs loading of the DNA damage checkpoint clamp to 5'-DNA junctions.  The Journal of biological chemistry.  2006 September. 281(38):27855-61.
[PubMed]

Parnell T, Kuhn E, Gilmore B, Helou C, Wold M, Geyer P.  Identification of genomic sites that bind the Drosophila suppressor of Hairy-wing insulator protein.  Molecular and cellular biology.  2006 August. 26(16):5983-93.
[PubMed]

Wold M, Rich A, Weeks D.  Deoxyribonucleic acid.  McGraw-Hill Encyclopedia of Science and Technology, 10th edition.  2006. DOI 10.1007/978-1-62703-032-8_15.

Binz S, Dickson A, Haring S, Wold M.  Functional assays for replication protein A (RPA).  Methods in enzymology.  2006. 409:11-38.
[PubMed]

Olson K, Narayanaswami P, Vise P, Lowry D, Wold M, Daughdrill G.  Secondary structure and dynamics of an intrinsically unstructured linker domain.  Journal of biomolecular structure & dynamics.  2005 October. 23(2):113-24.
[PubMed]

Vassin V, Wold M, Borowiec J.  Replication protein A (RPA) phosphorylation prevents RPA association with replication centers.  Molecular and cellular biology.  2004 March. 24(5):1930-43.
[PubMed]

Binz S, Sheehan A, Wold M.  Replication protein A phosphorylation and the cellular response to DNA damage.  DNA repair.  2004. 3:1015-24.
[PubMed]

Wyka I, Dhar K, Binz S, Wold M.  Replication protein A interactions with DNA: differential binding of the core domains and analysis of the DNA interaction surface.  Biochemistry.  2003 November. 42(44):12909-18.
[PubMed]

Binz S, Lao Y, Lowry D, Wold M.  The phosphorylation domain of the 32-kDa subunit of replication protein A (RPA) modulates RPA-DNA interactions. Evidence for an intersubunit interaction.  The Journal of biological chemistry.  2003 September. 278(37):35584-91.
[PubMed]

Daughdrill G, Buchko G, Botuyan M, Arrowsmith C, Wold M, Kennedy M, Lowry D.  Chemical shift changes provide evidence for overlapping single-stranded DNA- and XPA-binding sites on the 70 kDa subunit of human replication protein A.  Nucleic acids research.  2003 July. 31(14):4176-83.
[PubMed]

Shen J, Lao Y, Kamath-Loeb A, Wold M, Loeb L.  The N-terminal domain of the large subunit of human replication protein A binds to Werner syndrome protein and stimulates helicase activity.  Mechanisms of ageing and development.  2003. 124:921-30.
[PubMed]

Jackson D, Dhar K, Wahl J, Wold M, Borgstahl G.  Analysis of the human replication protein A:Rad52 complex: evidence for crosstalk between RPA32, RPA70, Rad52 and DNA.  Journal of molecular biology.  2002 August. 321(1):133-48.
[PubMed]

Mass G, Nethanel T, Lavrik O, Wold M, Kaufmann G.  Replication protein A modulates its interface with the primed DNA template during RNA-DNA primer elongation in replicating SV40 chromosomes.  Nucleic acids research.  2001 September. 29(18):3892-9.
[PubMed]

Daughdrill G, Ackerman J, Isern N, Botuyan M, Arrowsmith C, Wold M, Lowry D.  The weak interdomain coupling observed in the 70 kDa subunit of human replication protein A is unaffected by ssDNA binding.  Nucleic acids research.  2001 August. 29(15):3270-6.
[PubMed]

Kolpashchikov D, Khodyreva S, Khlimankov D, Wold M, Favre A, Lavrik O.  Polarity of human replication protein A binding to DNA.  Nucleic acids research.  2001 January. 29(2):373-9.
[PubMed]

Cho J, Song D, Bergeron J, Benlimame N, Wold M, Alaoui-Jamali M.  RBT1, a novel transcriptional co-activator, binds the second subunit of replication protein A.  Nucleic acids research.  2000 September. 28(18):3478-85.
[PubMed]

Rodrigo G, Roumagnac S, Wold M, Salles B, Calsou P.  DNA replication but not nucleotide excision repair is required for UVC-induced replication protein A phosphorylation in mammalian cells.  Molecular and cellular biology.  2000 April. 20(8):2696-705.
[PubMed]

Chan D, Son S, Block W, Ye R, Khanna K, Wold M, Douglas P, Goodarzi A, Pelley J, Taya Y, Lavin M, Lees-Miller S.  Purification and characterization of ATM from human placenta. A manganese-dependent, wortmannin-sensitive serine/threonine protein kinase.  The Journal of biological chemistry.  2000 March. 275(11):7803-10.
[PubMed]

Lao Y, Gomes X, Ren Y, Taylor J, Wold M.  Replication protein A interactions with DNA. III. Molecular basis of recognition of damaged DNA.  Biochemistry.  2000 February. 39(5):850-9.
[PubMed]

Buchko G, Daughdrill G, de Lorimier R, Rao B K, Isern N, Lingbeck J, Taylor J, Wold M, Gochin M, Spicer L, Lowry D, Kennedy M.  Interactions of human nucleotide excision repair protein XPA with DNA and RPA70 Delta C327: chemical shift mapping and 15N NMR relaxation studies.  Biochemistry.  1999 November. 38(46):15116-28.
[PubMed]

Chiang Y, Rizzino A, Sibenaller Z, Wold M, Vishwanatha J.  Specific down-regulation of annexin II expression in human cells interferes with cell proliferation.  Molecular and cellular biochemistry.  1999 September. 199:139-47.
[PubMed]

Jacobs D, Lipton A, Isern N, Daughdrill G, Lowry D, Gomes X, Wold M.  Human replication protein A: global fold of the N-terminal RPA-70 domain reveals a basic cleft and flexible C-terminal linker.  Journal of biomolecular NMR.  1999 August. 14(4):321-31.
[PubMed]

Pendergrass W, Gray M, Wold M, Luo P, Norwood T.  Analysis of the capacity of extracts from normal human young and senescent fibroblasts to support DNA synthesis in vitro.  Journal of cellular biochemistry.  1999 May. 73(2):176-87.
[PubMed]

Walther A, Gomes X, Lao Y, Lee C, Wold M.  Replication protein A interactions with DNA. 1. Functions of the DNA-binding and zinc-finger domains of the 70-kDa subunit.  Biochemistry.  1999 March. 38(13):3963-73.
[PubMed]

Lao Y, Lee C, Wold M.  Replication protein A interactions with DNA. 2. Characterization of double-stranded DNA-binding/helix-destabilization activities and the role of the zinc-finger domain in DNA interactions.  Biochemistry.  1999 March. 38(13):3974-84.
[PubMed]

Shao R, Cao C, Zhang H, Kohn K, Wold M, Pommier Y.  Replication-mediated DNA damage by camptothecin induces phosphorylation of RPA by DNA-dependent protein kinase and dissociates RPA:DNA-PK complexes.  The EMBO journal.  1999 March. 18(5):1397-406.
[PubMed]

Walther A, Wold M.  The eukaryotic replication fork.  Encyclopeida of Life Science. MacMillan Reference Limited, London.  1999. 

Walther A, Bjerke M, Wold M.  A novel assay for examining the molecular reactions at the eukaryotic replication fork: activities of replication protein A required during elongation.  Nucleic acids research.  1999 January. 27(2):656-64.
[PubMed]

Golub E, Gupta R, Haaf T, Wold M, Radding C.  Interaction of human rad51 recombination protein with single-stranded DNA binding protein, RPA.  Nucleic acids research.  1998 December. 26(23):5388-93.
[PubMed]

Sibenaller Z, Sorensen B, Wold M.  The 32- and 14-kilodalton subunits of replication protein A are responsible for species-specific interactions with single-stranded DNA.  Biochemistry.  1998 September. 37(36):12496-506.
[PubMed]

Gupta R, Golub E, Wold M, Radding C.  Polarity of DNA strand exchange promoted by recombination proteins of the RecA family.  Proceedings of the National Academy of Sciences of the United States of America.  1998 August. 95(17):9843-8.
[PubMed]

Wold M.  Deoxyribonucelic acid.  McGraw-Hill Encyclopedia of Science and Technology, 9th edition.  1998. 

Wold M.  Eukaryotic replication protein A.  Encyclopeida of Life Science. MacMillan Reference Limited, London.  1998. 

Lavrik O, Nasheuer H, Weisshart K, Wold M, Prasad R, Beard W, Wilson S, Favre A.  Subunits of human replication protein A are crosslinked by photoreactive primers synthesized by DNA polymerases.  Nucleic acids research.  1998 January. 26(2):602-7.
[PubMed]

Braun K, Lao Y, He Z, Ingles C, Wold M.  Role of protein-protein interactions in the function of replication protein A (RPA): RPA modulates the activity of DNA polymerase alpha by multiple mechanisms.  Biochemistry.  1997 July. 36(28):8443-54.
[PubMed]

Wold M.  Replication protein A: a heterotrimeric, single-stranded DNA-binding protein required for eukaryotic DNA metabolism.  Annual review of biochemistry.  1997. 66:61-92.
[PubMed]

Gomes X, Wold M.  Functional domains of the 70-kilodalton subunit of human replication protein A.  Biochemistry.  1996 August. 35(32):10558-68.
[PubMed]

Henricksen L, Carter T, Dutta A, Wold M.  Phosphorylation of human replication protein A by the DNA-dependent protein kinase is involved in the modulation of DNA replication.  Nucleic acids research.  1996 August. 24(15):3107-12.
[PubMed]

Tang C, Tomkinson A, Lane W, Wold M, Seto E.  Replication protein A is a component of a complex that binds the human metallothionein IIA gene transcription start site.  The Journal of biological chemistry.  1996 August. 271(35):21637-44.
[PubMed]

Gomes X, Henricksen L, Wold M.  Proteolytic mapping of human replication protein A: evidence for multiple structural domains and a conformational change upon interaction with single-stranded DNA.  Biochemistry.  1996 April. 35(17):5586-95.
[PubMed]

He Z, Henricksen L, Wold M, Ingles C.  RPA involvement in the damage-recognition and incision steps of nucleotide excision repair.  Nature.  1995 April. 374(6522):566-9.
[PubMed]

Gomes X, Wold M.  Structural analysis of human replication protein A. Mapping functional domains of the 70-kDa subunit.  The Journal of biological chemistry.  1995 March. 270(9):4534-43.
[PubMed]

Kim C, Wold M.  Recombinant human replication protein A binds to polynucleotides with low cooperativity.  Biochemistry.  1995 February. 34(6):2058-64.
[PubMed]

Kim C, Paulus B, Wold M.  Interactions of human replication protein A with oligonucleotides.  Biochemistry.  1994 November. 33(47):14197-206.
[PubMed]

Henricksen L, Wold M.  Replication protein A mutants lacking phosphorylation sites for p34cdc2 kinase support DNA replication.  The Journal of biological chemistry.  1994 September. 269(39):24203-8.
[PubMed]

Henricksen L, Umbricht C, Wold M.  Recombinant replication protein A: expression, complex formation, and functional characterization.  The Journal of biological chemistry.  1994 April. 269(15):11121-32.
[PubMed]

Kim C, Snyder R, Wold M.  Binding properties of replication protein A from human and yeast cells.  Molecular and cellular biology.  1992 July. 12(7):3050-9.
[PubMed]

Collins K, Erdile L, Randall S, Russo A, Simancek P, Umbricht C, Virshup D, Weinberg D, Wold M, Kelly T.  SV40 DNA replication with purified proteins: Functional interactions among the initiation proteins.  DNA Replication: The Regulatory Mechanisms.  1992. 

Weinberg D, Collins K, Simancek P, Russo A, Wold M, Virshup D, Kelly T.  Reconstitution of simian virus 40 DNA replication with purified proteins.  Proceedings of the National Academy of Sciences of the United States of America.  1990 November. 87(22):8692-6.
[PubMed]

Erdile L, Wold M, Kelly T.  The primary structure of the 32-kDa subunit of human replication protein A.  The Journal of biological chemistry.  1990 February. 265(6):3177-82.
[PubMed]

Wold M, Weinberg D, Virshup D, Li J, Kelly T.  Identification of cellular proteins required for simian virus 40 DNA replication.  The Journal of biological chemistry.  1989 February. 264(5):2801-9.
[PubMed]

Mensa-Wilmot K, Seaby, C, Wold M, Gomes B, McMacken R.  Reconstitution of nine-protein system that initiates bacteriophage lambda DNA replication.  The Journal of biological chemistry.  1989. 264:2853-2861.

Wold M, Kelly T.  Purification and characterization of replication protein A, a cellular protein required for in vitro replication of simian virus 40 DNA.  Proceedings of the National Academy of Sciences of the United States of America.  1988 April. 85(8):2523-7.
[PubMed]

Kelly T, Wold M, Li J.  Initiation of viral DNA replication.  Advances in virus research.  1988. 34:1-42.
[PubMed]

Kelly T, Rosenfeld P, Wides R, O'Neill E, Li J, Wold M.  Replication of adenovirus and SV40 chromosomes in vitro.  Philosophical transactions of the Royal Society of London. Series B, Biological sciences.  1987 December. 317(1187):429-38.
[PubMed]

Wold M, Li J, Kelly T.  Initiation of simian virus 40 DNA replication in vitro: large-tumor-antigen- and origin-dependent unwinding of the template.  Proceedings of the National Academy of Sciences of the United States of America.  1987 June. 84(11):3643-7.
[PubMed]

Yang L, Wold M, Li J, Kelly T, Liu L.  Roles of DNA topoisomerases in simian virus 40 DNA replication in vitro.  Proceedings of the National Academy of Sciences of the United States of America.  1987 February. 84(4):950-4.
[PubMed]

Li, J, Wold M, Kelly T.  Analysis of SV40 replication in vitro.  DNA Replication and Recombination.  1987. 

McMacken R, Alfano C, Gomes B, LeBowitz J, Mensa-Wilmot K, Roberts J, Wold M.  Biochemical mechanisms in the initiation of bacteriophage lambda DNA replication.  DNA Replication and Recombination.  1987. 

Wold M, Li J, Weinberg D, Virshup D, Sherley J, Verheyen E, Kelly T.  Cellular proteins required for SV40 DNA replication in vitro.  Cold Spring Harbor Cancer Cells Series.  1987. 6:133-141.

Yang L, Liu L, Li J, Wold M, Kelly T.  The roles of DNA topoisomerases in SV40 DNA replication.  DNA Replication and Recombination.  1987. 

McMacken R, Wold M, LeBowitz J, Roberts J, Mallory J, Wilkinson J.  Initiation of DNA replication in vitro promoted by the bacteriophage lambda O and P replication proteins.  Mechanisms of DNA Replication and Recombination.  1983. 

Wold M, Mallory J, Roberts J, LeBowitz J, McMacken R.  Initiation of bacteriophage lambda DNA replication in vitro with purified lambda replication proteins.  Proceedings of the National Academy of Sciences of the United States of America.  1982 October. 79(20):6176-80.
[PubMed]

Wold M, McMacken R.  Regulation of expression of the Escherichia coli dnaG gene and amplification of the dnaG primase.  Proceedings of the National Academy of Sciences of the United States of America.  1982 August. 79(16):4907-11.
[PubMed]

Date Last Modified: 06/07/2014 - 21:56:23