Picture of Johannes Walter
Johannes Walter, Ph.D.
Professor of Biological Chemistry and Molecular Pharmacology

We use ensemble and single molecule approaches in frog egg extracts to study mechanisms of DNA replication and DNA repair.

Research:

Vertebrate cells employ intricate mechanisms to duplicate their genomes and guard against DNA damage. Xenopus laevis frog egg extracts have an extraordinary capacity to recapitulate these processes in the test tube, allowing us to elucidate the underlying mechanisms.  Using this system, we study how the replicative DNA helicase unwinds DNA (Fu et al., Cell, 2011), how it is unloaded from chromatin during replication termination (Dewar et al., Nature 2015), and how its re-loading is prevented to limit replication to a single round per cell cycle (Havens et al., Mol Cell, 2009).  Using DNA templates containing chemically defined DNA lesions, we also examine the mechanism of replication-coupled repair, including DNA interstrand cross-link repair (Raschle et al., Cell, 2008) and DNA protein cross-link repair (Duxin et al., Cell 2014). In the last few years, we have begun to study replication and repair at the single molecule level (Yardimci et al., Nature, 2012; Graham et al., Mol Cell, 2016).  Finally, we examine how defects in replication-associated repair cause Fanconi anemia and other cancer pre-disposition syndromes (Long et al., Mol. Cell 2014; Knipscheer et al., Science 2009).

Address: 

Room SGM - 211

250 Longwood Avenue

Boston, MA 02115

Publications View
Mitotic CDK Promotes Replisome Disassembly, Fork Breakage, and Complex DNA Rearrangements.
Authors: Authors: Deng L, Wu RA, Sonneville R, Kochenova OV, Labib K, Pellman D, Walter JC.
Mol Cell
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TRAIP is a master regulator of DNA interstrand crosslink repair.
Authors: Authors: Wu RA, Semlow DR, Kamimae-Lanning AN, Kochenova OV, Chistol G, Hodskinson MR, Amunugama R, Sparks JL, Wang M, Deng L, Mimoso CA, Low E, Patel KJ, Walter JC.
Nature
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Extracts for Analysis of DNA Replication in a Nucleus-Free System.
Authors: Authors: Sparks J, Walter JC.
Cold Spring Harb Protoc
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The CMG Helicase Bypasses DNA-Protein Cross-Links to Facilitate Their Repair.
Authors: Authors: Sparks JL, Chistol G, Gao AO, Räschle M, Larsen NB, Mann M, Duxin JP, Walter JC.
Cell
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A single XLF dimer bridges DNA ends during nonhomologous end joining.
Authors: Authors: Graham TGW, Carney SM, Walter JC, Loparo JJ.
Nat Struct Mol Biol
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Replication Fork Reversal during DNA Interstrand Crosslink Repair Requires CMG Unloading.
Authors: Authors: Amunugama R, Willcox S, Wu RA, Abdullah UB, El-Sagheer AH, Brown T, McHugh PJ, Griffith JD, Walter JC.
Cell Rep
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CRL2Lrr1 promotes unloading of the vertebrate replisome from chromatin during replication termination.
Authors: Authors: Dewar JM, Low E, Mann M, Räschle M, Walter JC.
Genes Dev
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Ensemble and Single-Molecule Analysis of Non-Homologous End Joining in Frog Egg Extracts.
Authors: Authors: Graham TGW, Walter JC, Loparo JJ.
Methods Enzymol
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Replication-Dependent Unhooking of DNA Interstrand Cross-Links by the NEIL3 Glycosylase.
Authors: Authors: Semlow DR, Zhang J, Budzowska M, Drohat AC, Walter JC.
Cell
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Two-Stage Synapsis of DNA Ends during Non-homologous End Joining.
Authors: Authors: Graham TG, Walter JC, Loparo JJ.
Mol Cell
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