Anja K. Bielinsky, PhD

Professor, and Biophysics Department of Biochemistry, Molecular Biology

Anja K. Bielinsky

Contact Info

[email protected]

Office Phone 612-624-2469

Fax 612-624-0426

Lab Phone 612-624-0460

Office Address:
6-160 MCB
420 Washington Avenue SE
Minneapolis, MN 55455

Mailing Address:
Biochem, Molec Biol/Biophysics
Room 6-155 JacH
1214A (Campus Delivery Code)
321 Church St SE
Minneapolis, MN 55455

Lab Address:
6-212/218 MCB

Professor, and Biophysics Department of Biochemistry, Molecular Biology

Associate Dean for Foundational Science, Medical School

Associate Director for Basic Shared Resources, Masonic Cancer Center (MCC)

Preceptor, Medical Scientist Training Program (Combined MD/PhD Training Program)

Faculty, PhD Program in Biochemistry, Molecular Biology and Biophysics

Faculty, MS and PhD Programs in Pharmacology


Special Fellow, Leukemia and Lymphoma Society (1999-2001)

PhD, Heinrich Heine University, Düsseldorf, Germany, 1995

American Cancer Society Scholar (2002-2006),

Leukemia and Lymphoma Society Scholar (2008-2013)

Summary

Expertise

Regulation of DNA replication, Cell cycle, Cancer

Research

Research Summary/Interests

Eukaryotic cell proliferation and development requires a regulated DNA replication program to complete genome duplication. As S-phase proceeds, this program may be challenged by factors that impair DNA synthesis and cause replication stress. This, in turn, leads to the activation of complex networks that maintain genome stability and ensure cell division. When these networks are compromised cells experience aberrant DNA replication, increased mutation rate and chromosome instability. The combination of these events results in a variety of genetic diseases, including cancer and immune deficiencies. We model known patient mutations that interfere with genome maintenance in human tissue culture cells to uncover the molecular mechanism(s) underlying these diseases. Our lab utilizes a combination of cellular, molecular and bioinformatics tools to investigate how eukaryotic DNA replication is completed successfully with each round of the cell cycle and describe the damaging consequences that arise when replication does not proceed normally.

We believe that science is for everybody and we recognize that a diverse group strengthens our lab. We strive to create an inclusive environment for all lab members to succeed while being their full selves.

Research Methods/Techniques

For more details on our research projects, please visit: https://bielinsky.umn.edu/research-0

Publications

Congenital Diseases of DNA Replication: Clinical Phenotypes and Molecular Mechanisms
Schmit, M. and Bielinsky, A.K.
International Journal of Molecular Sciences, 2021 (pubmed)

SLFN11 promotes stalled fork degradation that underlies the phenotype in Fanconi anemia cells
Okamoto, Y., Abe, M., Mu, A., Tempaku, Y., Rogers, C.B., Mochizuki, A.L., Katsuki, Y., Kanemaki, M.T., Takaori-Kondo, A., Sobeck, A.T., Bielinsky, A.K., and Takata, M.
Blood, 2020 (pubmed)

PCNA-K164 ubiquitination facilitates origin licensing and mitotic DNA synthesis
Leung, W., Baxley, R.M., Thakar, T., Rogers, C.B., Buytendorp, J.P., Wang, L., Tella, A., Moldovan, G.L., Shima, S., and Bielinsky, A.K.
bioRxiv, 2020(bioRxiv)

Bi-allelic MCM10 mutations cause telomere shortening with immune dysfunction and cardiomyopathy.
Baxley, R.M., Leung, W., Schmit, M.M., Matson, J.P., Oram, M.K., Wang, L., Taylor, J., Yin, L., Hedberg, J., Rogers, C.B., Harvey, A.J., Basu, D., Taylor, J.C., Pagnamenta, A.T., Dreau, H., Craft, J., Ormondroyd, E., Watkins, H, Hendrickson, E.A., Mace, E.M., Orange, J.S., Aihara, H., Stewart, G.S., Blair, E., Cook, J.G., and Bielinsky, A.K.
bioRxiv, 2020 (bioRxiv)

Human NK cell deficiency as a result of biallelic mutations in MCM10.
Mace, E.M., Paust, S., Conte, M.I., Baxley, R.M., Schmit, M., Guilz, N.C., Mukherjee, M., Pezzi, A.E., Chmielowiec, J., Tatineni, S., Chinn, I.K., Coban Akdemir, Z., Jhangiani, S.N., Muzny, D.M., Stray-Pedersen, A., Bradley, R.E., Moody, M., Connor, P.P., Heaps, A.G., Steward, C., Banerjee, P.P., Gibbs, R.A., Borowiak, M., Lupski, J.R., Jolles, S., Bielinsky, A.K., and Orange, J.S.
Journal of Clinical Investigation, 2020 (pubmed)

Ubiquitinated-PCNA protects replication forks from DNA2-mediated degradation by regulating Okazaki fragment maturation and chromatin assembly.
Thakar, T., Leung, W., Nicolae, C.M., Clements, K.E., Shen, B., Bielinsky, A.K., and Moldovan, G.L.
Nature Communications, 2020 (pubmed)

EXO1 resection at G-quadruplex structures facilitates resolution and replication.
Stroik, S., Kurtz, K., Lin, K., Karachenets, S., Myers, C.L., Bielinsky, A.K., and Hendrickson, E.A.
Nucleic Acids Research, 2020 (pubmed)

Functional crosstalk between the Fanconi anemia and ATRX/DAXX histone chaperone pathways promotes replication fork recovery.
Raghunandan, M., Yeo, J.E., Walter, R., Saito, K., Harvey, A.J., Ittershagen, S., Lee, E.A., Yang, J., Hoatlin, M.E., Bielinsky, A.K., Hendrickson, E.A., Schärer, O., and Sobeck, A.
Human Molecular Genetics, 2020 (pubmed)

The anti-parasitic agent suramin and several of its analogues are inhibitors of the DNA binding protein Mcm10.
Paulson, C.N., John, K., Baxley, R.M., Kurniawan, F., Orellana, K., Francis, R., Sobeck, A., Eichman, B.F., Chazin, W.J., Aihara, H., Georg, G.I., Hawkinson, J.E., and Bielinsky, A.K.
Open Biology, 2019 (pubmed)

Mechanisms of DNA Damage Tolerance: Post-Translational Regulation of PCNA.
Leung, W., Baxley, R.M., Moldovan, G.L., and Bielinsky, A.K.
Genes, 2018 (pubmed)

Crystal Structure of Entamoeba histolytica Cdc45 Suggests a Conformational Switch that May Regulate DNA Replication.
Kurniawan, F., Shi, K., Kurahashi, K., Bielinsky, A.K., and Aihara, H.
iScience, 2018 (pubmed)

Flap endonuclease overexpression drives genome instability and DNA damage hypersensitivity in a PCNA-dependent manner.
Becker, J.R., Gallo, D., Leung, W., Croissant, T., Thu, Y.M., Nguyen, H.D., Starr, T.K., Brown, G.W., and Bielinsky, A.K.
Nucleic Acids Research, 2018 (pubmed)

Rapid DNA replication origin licensing protects stem cell pluripotency.
Matson, J.P., Dumitru, R., Coryell, P., Baxley, R.M., Chen, W., Twaroski, K., Webber, B.R., Tolar, J., Bielinsky, A.K., Purvis, J.E., and Cook, J.G.
eLife, 2017 (pubmed)

Mcm10: A Dynamic Scaffold at Eukaryotic Replication Forks.
Baxley, R.M. and Bielinsky, A.K.
Genes, 2017 (pubmed)

Not just for coding: a new role for histone tails in replication enzyme activation.
Bielinsky, A.K. and Leung, W.
FEBS Journal, 2016 (pubmed)

Mapping ubiquitination sites of S. cerevisiae Mcm10.
Zhang, T., Fultz, B.L., Das-Bradoo, S., and Bielinsky, A.K.
Biochemistry and Biophysics Reports, 2016 (pubmed)

Mcm10: The glue at replication forks.
Bielinsky, A.K.
Cell Cycle, 2016 (pubmed)

Slx5/Slx8 promotes replication stress tolerance by facilitating mitotic progression.
Thu, Y.M., Van Riper, S., Higgins, L.A., Zhang, T., Becker, J., Markowski, T., Nguyen, H.D., Griffin, T., and Bielinsky, A.K.
Cell Reports, 2016 (pubmed)

Penetrating enemy territory: soluble PCNA-peptides stress out MYCN-overexpressing neuroblastomas.
Bielinsky, A.K.
EBioMedicine, 2015 (pubmed)

Genetic interactions implicating postreplicative repair in Okazaki fragment processing.
Becker, J.R., Pons, C., Nguyen, H.D., Constanzo, M., Boone, C., Myers, C.L., and Bielinsky, A.K.
PLOS Genetics, 2015 (pubmed)

eIF4E Threshold Levels Differ in Governing Normal and Neoplastic Expansion of Mammary Stem and Luminal Progenitor Cells.
Adulov, S., Herrera, J., Smith, K., Peterson, M., Gomez-Garcia, J., Beadnell, T., Schwertfeger, K., Benyumov, A., Manivel, J.C., Li, S., Bielinsky, A.K., Yee, D., Bitterman, P., and Polunovsky, V.
Cancer Research, 2015 (pubmed)

The N-terminus of Mcm10 is important for interaction with the 9-1-1 clamp and in resistance to DNA damage.
Alver, R.C., Zhang, T., Josephrajan, A., Fultz, B.L., Hendrix, C.J., Das-Dradoo, S., and Bielinsky, A.K.
Nucleic Acids Research, 2014 (pubmed)

Mcm10 deficiency causes defective-replisome-induced mutagenesis and a dependency on postreplicative repair.
Becker, J.R., Nguyen, H.D., Wang, X., and Bielinsky, A.K.
Cell Cycle, 2014 (pubmed)

Mcm10: one tool for all – integrity, maintenance and damage control.
Thu, Y.M. and Bielinsky, A.K.
Seminars in Cell and Developmental Biology, 2014 (pubmed)

RNF4 and PLK1 are required for replication fork collapse in ATR-deficient cells.
Ragland, R. L., Patel, S., Revard, R., Smith, K., Peters, A.A., Bielinsky, A.K., and Brown, E.J.
Genes & Development, 2013 (pubmed)

Enigmatic roles of Mcm10 in DNA replication.
Thu, Y.M. and Bielinsky, A.K.
Trends in Biochemical Sciences, 2013 (pubmed)

Unligated Okazaki fragments induce PCNA ubiquitination and a requirement for Rad59-dependent replication fork progression.
Nguyen, H.D., Becker, J., Thu, Y.M., Costanzo, M., Koch, E.N., Smith, S., Myung, K., Myers, C.L., Boone, C., and Bielinsky, A.K.
PLoS ONE, 2013 (pubmed)

Mcm10 self-association is mediated by an N-terminal coiled-coil domain.
Du, W., Josephrajan, A., Adhikary, S., Bowles, T., Bielinsky, A.K., and Eichman, B.
PLoS ONE, 2013 (pubmed)

Ubc4 and Not4 regulate steady-state levels of DNA polymerase-alpha to promote efficient and accurate DNA replication.
Haworth, J.C., Alver, R., Anderson, M., and Bielinsky, A.K.
Molecular Biology of the Cell, 2010 (pubmed)

HDM2 ERKs PCNA.
Nguyen, H.D. and Bielinsky, A.K.
Journal of Cell Biology, 2010 (pubmed)

Termination at sTop2.
Alver, R. and Bielinsky, A.K.
Molecular Cell, 2010(pubmed)

Damage-specific modification of PCNA.
Das-Bradoo, S., Nguyen, H.D., and Bielinsky, A.K.
Cell Cycle, 2010 (pubmed)

Defects in DNA ligase I triggers PCNA ubiquitylation at Lys 107.
Das-Bradoo, S., Nguyen, H.D., Ricke, R.M., Haworth, J.C., and Bielinsky, A.K.
Nature Cell Biology, 2010 (pubmed)

Developmental origins of cancer.
Johnson, K.J., Springer, N.M., Bielinsky, A.K., Largaespada, D.A., and Ross, J.A.
Cancer Research, 2009 (pubmed)

Das-Bradoo, S. and Bielinsky, A.K.
Molecular Methods in DNA Replication, 2009 (pubmed)
Analyzing origin activation patterns by copy-number change experiments.

Raveendranathan, M. and Bielinsky, A.K.
Molecular Methods in DNA Replication, 2009 (pubmed)

Structural basis for DNA binding by replication initiator Mcm10.
Warren, E., Vaithiyalingam, S., Haworth, J., Greer, B., Smith, J., Bielinsky, A.K., Chazin, W. and Eichman, B.
Structure, 2008 (pubmed)

Scarce but scary.
Bielinsky, A.K.
Nature Genetics, 2007 (pubmed)

Human Mcm10 regulates the catalytic subunit of DNA polymerase-alpha and prevents DNA damage during replication.
Chattopadhyay, S. and Bielinsky, A. K.
Molecular Biology of the Cell, 2007 (pubmed)

The spatial arrangement of ORC binding modules determines the functionality of replication origins in budding yeast.
Bolon, Y.T. and Bielinsky, A.K.
Nucleic Acids Research, 2006 (pubmed)

Genome-wide replication profiles of S phase checkpoint mutants reveal fragile sites in yeast.
Raveendranathan, M., Chattopadhyay, S., Bolon, Y.T., Haworth, J.C., Clarke, D.J., and Bielinsky, A.K.
EMBO Journal, 2006 (pubmed)

A conserved Hsp10-like domain in Mcm10 is required for the stabilization of DNA polymerase-alpha in budding yeast.
Ricke, R.M. and Bielinsky, A.K.
Journal of Biological Chemistry, 2006 (pubmed)

Interaction between PCNA and di-ubiquitinated Mcm10 is essential for cell growth in budding yeast.
Das-Bradoo, S., Ricke, R.M. and Bielinsky, A.K.
Molecular & Cell Biology, 2006 (pubmed)

Encircled: large-scale purification of replication origins from mammalian chromosomes.
Bielinsky, A.K. and Raveendranathan, M.
Molecular Cell, 2006(pubmed)

Easy detection of chromatin binding proteins by the histone association assay.
Ricke, R.M. and Bielinsky, A.K.
Biological Procedures Online, 2005 (pubmed)

Mcm10 regulates the stability and chromatin association of DNA polymerase-alpha.
Ricke, R.M. and Bielinsky, A.K.
Molecular Cell, 2004 (pubmed)

Replication origins-why do we need so many?
Bielinsky, A.K.
Cell Cycle, 2003 (pubmed)

DNA replication and chromatin.
Gerbi, S.A. and Bielinsky, A.K.
Current Opinion in Genetics and Development, 2002(pubmed)

Origin recognition complex binding to a metazoan replication origin.
Bielinsky, A.K., Blitzblau, H., Beall, E.L., Ezrokhi, M., Smith, H.S., Botchan, M.R., and Gerbi, S.A.
Current Biology, 2001 (pubmed)

Where it all starts: eukaryotic origins of DNA replication.
Bielinsky, A.K. and Gerbi, S.A.
Journal of Cell Science, 2001 (pubmed)

Chromosomal ARS1 has a single leading strand start site.
Bielinsky, A.K. and Gerbi, S.A.
Molecular Cell, 1999(pubmed)

Methods to map origins of replication in eukaryotes in "Eukaryotic DNA Replication: a practical approach"
Gerbi, S.A., Bielinsky, A.K., Liang, C., Lunyak, V.V., and Urnov, F.D.
Oxford University Press, (ed., S. Cotterill), 1999

Discrete start sites for DNA synthesis in the yeast ARS1 origin.
Bielinsky, A.K. and Gerbi, S.A.
Science, 1998 (pubmed)

Replication initiation point mapping.
Gerbi, S.A. and Bielinsky, A.K. 1997.
Methods, 1997 (pubmed)