Hannah L Klein

Biosketch / Results /

Hannah L Klein, Ph.D.

Professor; Interim Chair & Professor
Departments of Biochemistry and Molecular Pharmacology, Medicine (Administration) and Pathology

Contact Info

Address
550 First Avenue
Floor 3 Room 367
Medical Science Building
New York, NY 10016

212-263-5778
212-263-8166
Hannah.Klein@nyumc.org


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Education

1971-1976 — University of Washington, Seattle, PhD in Genetics, Graduate Education
1976-1979 — Princeton University, Microbiology, PostDoctoral Training
1979-1981 — University of Chicago, Biochemistry, PostDoctoral Training

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Research Summary

Genome Instability and DNA Damage Checkpoints

We have found that defects in DNA repair genes result in the accumulation of spontaneous DNA damage that partially or completely arrests cells during or after DNA replication. This block can be overcome by mutating DNA damage checkpoint genes. We believe the DNA damage that accumulates spontaneously leads to a replication block and is the result of an attempt to repair collapsed replication forks or other replication blocks through homologous recombination. Our studies point to MEC1 (ATR) as a key molecule that signals the presence of unrepaired DNA damage. We are currently looking at the effect of the Mec1 signal on DNA replication in our mutants. Although loss of the Mec1 kinase permits cells with unrepaired damage to grow better, the cost to the cell is an greatly increased rate of chromosome loss. We are studying this process as a model for the spontaneous loss of heterozygosity seen in many tumor cells.

Genome Instability and Reduced Life Span

A second project in the lab is focused on a novel RNA polymerase II complex component. We initially identified the HPR1 gene through a mutant screen for strains that showed increased instability of repeated DNA sequences. The HPR1 gene turned out to encode a topoisomerase-like gene that is part of a RNA polymerase II complex. When cells are deficient in this gene they become unstable for repeated sequences and this has been shown to be the direct result of transcription elongation defects. These cells also have a reduced life span, linking transcription to aging. We have identified suppressors the of genome instability of hpr1 mutants. These suppressors also suppress the life span reduction phenotype of the hpr1 mutants.

Research Interests

Pathways of DNA damage avoidance, DNA repair and recombination, genomic instability, DNA damage checkpoints

Research Keywords

DNA helicases, DNA recombination, DNA repair, genome stability,DNA damage checkpoints

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All data from NYU Health Sciences Library Faculty Bibliography — -

Contact:
http://hsl.med.nyu.edu/faculty-bibliography-search

Avoidance of ribonucleotide-induced mutations by RNase H2 and Srs2-Exo1 mechanisms
Potenski, Catherine J; Niu, Hengyao; Sung, Patrick; Klein, Hannah L
2014 Jul;511(7508):251-254, Nature
— id: 1102852, year: 2014, vol: 511, page: 251, stat: Journal Article,

The PCNA Interaction Protein Box Sequence in Rad54 Is an Integral Part of Its ATPase Domain and Is Required for Efficient DNA Repair and Recombination
Burgess, Rebecca C; Sebesta, Marek; Sisakova, Alexandra; Marini, Victoria P; Lisby, Michael; Damborsky, Jiri; Klein, Hannah; Rothstein, Rodney; Krejci, Lumir
2013 ;8(12):e82630-e82630 e82630, PLoS one
— id: 741022, year: 2013, vol: 8, page: e82630, stat: Journal Article,

Tid1/Rdh54 translocase is phosphorylated through a Mec1- and Rad53-dependent manner in the presence of DSB lesions in budding yeast
Ferrari, Matteo; Nachimuthu, Benjamin Tamilselvan; Donnianni, Roberto Antonio; Klein, Hannah; Pellicioli, Achille
2013 May;12(5):347-355, DNA repair (Amsterdam)
— id: 348812, year: 2013, vol: 12, page: 347, stat: Journal Article,

Death becomes her: FBH1, DNA damage and apoptosis
Potenski, Catherine J; Klein, Hannah L
2013 May;12(9):1336-1336, Cell cycle
— id: 335592, year: 2013, vol: 12, page: 1336, stat: Journal Article,

Characterization of the Interaction between the Saccharomyces cerevisiae Rad51 Recombinase and the DNA Translocase Rdh54
Santa Maria, Sergio R; Kwon, Youngho; Sung, Patrick; Klein, Hannah L
2013 Jul;288(30):21999-22005, Journal of biological chemistry
— id: 463562, year: 2013, vol: 288, page: 21999, stat: Journal Article,

A Variant of the Breast Cancer Type 2 Susceptibility Protein (BRC) Repeat Is Essential for the RECQL5 Helicase to Interact with RAD51 Recombinase for Genome Stabilization
Islam, M Nurul; Paquet, Nicolas; Fox, David 3rd; Dray, Eloise; Zheng, Xiao-Feng; Klein, Hannah; Sung, Patrick; Wang, Weidong
2012 Jul;287(28):23808-23818, Journal of biological chemistry
— id: 174444, year: 2012, vol: 287, page: 23808, stat: Journal Article,

Sgs1-the maestro of recombination
Klein, Hannah L; Symington, Lorraine S
2012 Apr;149(2):257-259, Cell
— id: 164366, year: 2012, vol: 149, page: 257, stat: Journal Article,

The replication checkpoint protects fork stability by releasing transcribed genes from nuclear pores
Bermejo, Rodrigo; Capra, Thelma; Jossen, Rachel; Colosio, Arianna; Frattini, Camilla; Carotenuto, Walter; Cocito, Andrea; Doksani, Ylli; Klein, Hannah; Gomez-Gonzalez, Belen; Aguilera, Andres; Katou, Yuki; Shirahige, Katsuhiko; Foiani, Marco
2011 Jul 22;146(2):233-246, Cell
— id: 136488, year: 2011, vol: 146, page: 233, stat: Journal Article,

Analyses of the yeast Rad51 recombinase A265V mutant reveal different in vivo roles of Swi2-like factors
Chi, Peter; Kwon, Youngho; Visnapuu, Mari-Liis; Lam, Isabel; Santa Maria, Sergio R; Zheng, Xiuzhong; Epshtein, Anastasiya; Greene, Eric C; Sung, Patrick; Klein, Hannah L
2011 Aug;39(15):6511-6522, Nucleic acids research
— id: 136937, year: 2011, vol: 39, page: 6511, stat: Journal Article,

The role of Candida albicans homologous recombination factors Rad54 and Rdh54 in DNA damage sensitivity
Hoot, Samantha J; Zheng, Xiuzhong; Potenski, Catherine J; White, Theodore C; Klein, Hannah L
2011 ;11:214-214, BMC microbiology
— id: 139736, year: 2011, vol: 11, page: 214, stat: Journal Article,

Molecular biology: The expanding arena of DNA repair
Potenski, Catherine J; Klein, Hannah L
2011 Mar 3;471(7336):48-49, Nature
— id: 134138, year: 2011, vol: 471, page: 48, stat: Journal Article,

R we there yet? R-loop hazards to finishing the journey
Potenski, Catherine J; Klein, Hannah L
2011 Dec;44(6):848-850, Molecular cell
— id: 155640, year: 2011, vol: 44, page: 848, stat: Journal Article,

Methods to study mitotic homologous recombination and genome stability
Zheng, Xiuzhong; Epstein, Anastasiya; Klein, Hannah L
2011 ;745:3-13, Methods in molecular biology
— id: 134456, year: 2011, vol: 745, page: 3, stat: Journal Article,

Cdk1 targets Srs2 to complete synthesis-dependent strand annealing and to promote recombinational repair
Saponaro, Marco; Callahan, Devon; Zheng, Xiuzhong; Krejci, Lumir; Haber, James E; Klein, Hannah L; Liberi, Giordano
2010 Feb;6(2):e1000858-e1000858, PLoS genetics
— id: 107900, year: 2010, vol: 6, page: e1000858, stat: Journal Article,

Swi2/Snf2-related translocases prevent accumulation of toxic Rad51 complexes during mitotic growth
Shah, Parisha P; Zheng, Xiuzhong; Epshtein, Anastasiya; Carey, Jeffrey N; Bishop, Douglas K; Klein, Hannah L
2010 Sep 24;39(6):862-872, Molecular cell
— id: 147665, year: 2010, vol: 39, page: 862, stat: Journal Article,

Functional interactions of meiotic recombination factors Rdh54 and Dmc1
Chi, Peter; Kwon, Youngho; Moses, Dana N; Seong, Changhyun; Sehorn, Michael G; Singh, Akhilesh K; Tsubouchi, Hideo; Greene, Eric C; Klein, Hannah L; Sung, Patrick
2009 Feb 1;8(2):279-284, DNA repair (Amsterdam)
— id: 107905, year: 2009, vol: 8, page: 279, stat: Journal Article,

Functional significance of the Rad51-Srs2 complex in Rad51 presynaptic filament disruption
Colavito, Sierra; Macris-Kiss, Margaret; Seong, Changhyun; Gleeson, Olive; Greene, Eric C; Klein, Hannah L; Krejci, Lumir; Sung, Patrick
2009 Nov;37(20):6754-6764, Nucleic acids research
— id: 107901, year: 2009, vol: 37, page: 6754, stat: Journal Article,

Breaking up just got easier to do
Klein, Hannah L; Symington, Lorraine S
2009 Jul 10;138(1):20-22, Cell
— id: 100674, year: 2009, vol: 138, page: 20, stat: Journal Article,

Yeast Mph1 helicase dissociates Rad51-made D-loops: implications for crossover control in mitotic recombination
Prakash, Rohit; Satory, Dominik; Dray, Eloise; Papusha, Almas; Scheller, Jurgen; Kramer, Wilfried; Krejci, Lumir; Klein, Hannah; Haber, James E; Sung, Patrick; Ira, Grzegorz
2009 Jan 1;23(1):67-79, Genes & development
— id: 107904, year: 2009, vol: 23, page: 67, stat: Journal Article,

Structural transitions within human Rad51 nucleoprotein filaments
Robertson, Ragan B; Moses, Dana N; Kwon, YoungHo; Chan, Pamela; Chi, Peter; Klein, Hannah; Sung, Patrick; Greene, Eric C
2009 Aug 4;106(31):12688-12693, Proceedings of the National Academy of Sciences of the United States of America
— id: 107902, year: 2009, vol: 106, page: 12688, stat: Journal Article,

Visualizing the disassembly of S. cerevisiae Rad51 nucleoprotein filaments
Robertson, Ragan B; Moses, Dana N; Kwon, YoungHo; Chan, Pamela; Zhao, Weixing; Chi, Peter; Klein, Hannah; Sung, Patrick; Greene, Eric C
2009 May 15;388(4):703-720, Journal of molecular biology
— id: 107903, year: 2009, vol: 388, page: 703, stat: Journal Article,

Molecular biology: DNA endgames
Klein, Hannah L
2008 Oct 9;455(7214):740-741, Nature
— id: 97749, year: 2008, vol: 455, page: 740, stat: Journal Article,

The consequences of Rad51 overexpression for normal and tumor cells
Klein, Hannah L
2008 May 3;7(5):686-693, DNA repair (Amsterdam)
— id: 80301, year: 2008, vol: 7, page: 686, stat: Journal Article,

ATP-dependent chromatin remodeling by the Saccharomyces cerevisiae homologous recombination factor Rdh54
Kwon, YoungHo; Seong, Changhyun; Chi, Peter; Greene, Eric C; Klein, Hannah; Sung, Patrick
2008 Apr 18;283(16):10445-10452, Journal of biological chemistry
— id: 107906, year: 2008, vol: 283, page: 10445, stat: Journal Article,

Mechanism of eukaryotic homologous recombination
San Filippo, Joseph; Sung, Patrick; Klein, Hannah
2008 ;77:229-257, Annual review of biochemistry
— id: 107907, year: 2008, vol: 77, page: 229, stat: Journal Article,

Reversal of fortune: Rad5 to the rescue
Klein, Hannah L
2007 Oct 26;28(2):181-183, Molecular cell
— id: 75480, year: 2007, vol: 28, page: 181, stat: Journal Article,

DNA helicases in recombination
Klein, HL
2007 ;17:1-26, Topics in current genetics
— id: 644362, year: 2007, vol: 17, page: 1, stat: Journal Article,

Synergistic action of the Saccharomyces cerevisiae homologous recombination factors Rad54 and Rad51 in chromatin remodeling
Kwon, Youngho; Chi, Peter; Roh, Dong Hyun; Klein, Hannah; Sung, Patrick
2007 Oct 1;6(10):1496-1506, DNA repair (Amsterdam)
— id: 107908, year: 2007, vol: 6, page: 1496, stat: Journal Article,

Yeast recombination factor Rdh54 functionally interacts with the Rad51 recombinase and catalyzes Rad51 removal from DNA
Chi, Peter; Kwon, Youngho; Seong, Changhyun; Epshtein, Anastasiya; Lam, Isabel; Sung, Patrick; Klein, Hannah L
2006 Sep 8;281(36):26268-26279, Journal of biological chemistry
— id: 67273, year: 2006, vol: 281, page: 26268, stat: Journal Article,

A SUMOry of DNA replication: synthesis, damage, and repair
Klein, Hannah L
2006 Nov 3;127(3):455-457, Cell
— id: 69601, year: 2006, vol: 127, page: 455, stat: Journal Article,

Mechanism of homologous recombination: mediators and helicases take on regulatory functions
Sung, Patrick; Klein, Hannah
2006 Oct;7(10):739-750, Nature reviews. Molecular cell biology
— id: 107909, year: 2006, vol: 7, page: 739, stat: Journal Article,

Biochemical and genetic characterization of Hmi1p, a yeast DNA helicase involved in the maintenance of mitochondrial DNA
Monroe, Danny S Jr; Leitzel, Adelaide K; Klein, Hannah L; Matson, Steven W
2005 Dec;22(16):1269-1286, Yeast
— id: 67274, year: 2005, vol: 22, page: 1269, stat: Journal Article,

Role of ATP hydrolysis in the antirecombinase function of Saccharomyces cerevisiae Srs2 protein
Krejci, Lumir; Macris, Margaret; Li, Ying; Van Komen, Stephen; Villemain, Jana; Ellenberger, Thomas; Klein, Hannah; Sung, Patrick
2004 May 28;279(22):23193-23199, Journal of biological chemistry
— id: 67276, year: 2004, vol: 279, page: 23193, stat: Journal Article,

Effects of tumor-associated mutations on Rad54 functions
Smirnova, Marina; Van Komen, Stephen; Sung, Patrick; Klein, Hannah L
2004 Jun 4;279(23):24081-24088, Journal of biological chemistry
— id: 48199, year: 2004, vol: 279, page: 24081, stat: Journal Article,

Mrc1 is required for sister chromatid cohesion to aid in recombination repair of spontaneous damage
Xu, Hong; Boone, Charles; Klein, Hannah L
2004 Aug;24(16):7082-7090, Molecular & cellular biology
— id: 67275, year: 2004, vol: 24, page: 7082, stat: Journal Article,

DNA helicase Srs2 disrupts the Rad51 presynaptic filament
Krejci, Lumir; Van Komen, Stephen; Li, Ying; Villemain, Jana; Reddy, Mothe Sreedhar; Klein, Hannah; Ellenberger, Thomas; Sung, Patrick
2003 May 15;423(6937):305-309, Nature
— id: 36568, year: 2003, vol: 423, page: 305, stat: Journal Article,

ATPase and DNA Helicase Activities of the Saccharomyces cerevisiae Anti-recombinase Srs2
Van Komen, Stephen; Reddy, Mothe Sreedhar; Krejci, Lumir; Klein, Hannah; Sung, Patrick
2003 Nov 7;278(45):44331-44337, Journal of biological chemistry
— id: 39080, year: 2003, vol: 278, page: 44331, stat: Journal Article,

Replication, recombination, and repair: going for the gold
Klein, Hannah L; Kreuzer, Kenneth N
2002 Mar;9(3):471-480, Molecular cell
— id: 27572, year: 2002, vol: 9, page: 471, stat: Journal Article,

hpr1Delta affects ribosomal DNA recombination and cell life span in Saccharomyces cerevisiae
Merker, Robert J; Klein, Hannah L
2002 Jan;22(2):421-429, Molecular & cellular biology
— id: 26519, year: 2002, vol: 22, page: 421, stat: Journal Article,

High-Copy-Number Expression of Sub2p, a Member of the RNA Helicase Superfamily, Suppresses hpr1-Mediated Genomic Instability
Fan HY; Merker RJ; Klein HL
2001 Aug;21(16):5459-5470, Molecular & cellular biology
— id: 21106, year: 2001, vol: 21, page: 5459, stat: Journal Article,

Mutations in Recombinational Repair and in Checkpoint Control Genes Suppress the Lethal Combination of srs2Delta With Other DNA Repair Genes in Saccharomyces cerevisiae
Klein HL
2001 Feb;157(2):557-565, Genetics
— id: 17562, year: 2001, vol: 157, page: 557, stat: Journal Article,

Requirement for the SRS2 DNA helicase gene in non-homologous end joining in yeast
Hegde V; Klein H
2000 Jul 15;28(14):2779-2783, Nucleic acids research
— id: 11585, year: 2000, vol: 28, page: 2779, stat: Journal Article,

A radical solution to death
Klein HL
2000 Jun;25(2):132-134, Nature genetics
— id: 17414, year: 2000, vol: 25, page: 132, stat: Journal Article,

Promotion of Rad51-dependent D-loop formation by yeast recombination factor Rdh54/Tid1
Petukhova, G; Sung, P; Klein, H
2000 Sep 1;14(17):2206-2215, Genes & development
— id: 147667, year: 2000, vol: 14, page: 2206, stat: Journal Article,

A novel cold-sensitive allele of the rate-limiting enzyme of fatty acid synthesis, acetyl coenzyme A carboxylase, affects the morphology of the yeast vacuole through acylation of Vac8p
Schneiter R; Guerra CE; Lampl M; Tatzer V; Zellnig G; Klein HL; Kohlwein SD
2000 May;20(9):2984-2995, Molecular & cellular biology
— id: 17415, year: 2000, vol: 20, page: 2984, stat: Journal Article,

A complex containing RNA polymerase II, Paf1p, Cdc73p, Hpr1p, and Ccr4p plays a role in protein kinase C signaling
Chang M; French-Cornay D; Fan HY; Klein H; Denis CL; Jaehning JA
1999 Feb;19(2):1056-1067, Molecular & cellular biology
— id: 7937, year: 1999, vol: 19, page: 1056, stat: Journal Article,

Yeast Rad54 promotes Rad51-dependent homologous DNA pairing via ATP hydrolysis-driven change in DNA double helix conformation
Petukhova G; Van Komen S; Vergano S; Klein H; Sung P
1999 Oct 8;274(41):29453-29462, Journal of biological chemistry
— id: 20352, year: 1999, vol: 274, page: 29453, stat: Journal Article,

The Saccharomyces cerevisiae hyperrecombination mutant hpr1Delta is synthetically lethal with two conditional alleles of the acetyl coenzyme A carboxylase gene and causes a defect in nuclear export of polyadenylated RNA
Schneiter R; Guerra CE; Lampl M; Gogg G; Kohlwein SD; Klein HL
1999 May;19(5):3415-3422, Molecular & cellular biology
— id: 8509, year: 1999, vol: 19, page: 3415, stat: Journal Article,

Prefoldin, a chaperone that delivers unfolded proteins to cytosolic chaperonin
Vainberg IE; Lewis SA; Rommelaere H; Ampe C; Vandekerckhove J; Klein HL; Cowan NJ
1998 May 29;93(5):863-873, Cell
— id: 7835, year: 1998, vol: 93, page: 863, stat: Journal Article,

RDH54, a RAD54 homologue in Saccharomyces cerevisiae, is required for mitotic diploid-specific recombination and repair and for meiosis
Klein HL
1997 Dec;147(4):1533-1543, Genetics
— id: 12190, year: 1997, vol: 147, page: 1533, stat: Journal Article,

Mutations in the RNA polymerase II transcription machinery suppress the hyperrecombination mutant hpr1 delta of Saccharomyces cerevisiae
Fan HY; Cheng KK; Klein HL
1996 Mar;142(3):749-759, Genetics
— id: 8417, year: 1996, vol: 142, page: 749, stat: Journal Article,

MUTATIONS IN BASAL TRANSCRIPTION FACTORS SUPPRESS THE HPR1 HYPERREC MUTANT OF YEAST
FAN, HY; KLEIN, H
1995 MAR 10 ;14(1-6):312-312, Journal of cellular biochemistry
— id: 86748, year: 1995, vol: 14, page: 312, stat: Journal Article,

Examination of mitotic recombination by means of hyper-recombination mutants in Saccharomyces cerevisiae
Klein HL
1995 ;51:271-303, Progress in nucleic acid research & molecular biology
— id: 6836, year: 1995, vol: 51, page: 271, stat: Journal Article,

Genetic control of intrachromosomal recombination
Klein HL
1995 Feb;17(2):147-159, Bioessays
— id: 8064, year: 1995, vol: 17, page: 147, stat: Journal Article,

RECOMBINATION IN YEAST AND ITS RELATIONSHIP TO DNA-REPAIR
KLEIN, HL; FAN, HY; CHANG, K; DIMOVA, D; THANGAVELU, A; DEMURO, MA
1995 MAR 10 ;14(1-6):269-269, Journal of cellular biochemistry
— id: 86746, year: 1995, vol: 14, page: 269, stat: Journal Article,

Characterization of mutations that suppress the temperature-sensitive growth of the hpr1 delta mutant of Saccharomyces cerevisiae
Fan HY; Klein HL
1994 Aug;137(4):945-956, Genetics
— id: 6612, year: 1994, vol: 137, page: 945, stat: Journal Article,

Purification and characterization of the SRS2 DNA helicase of the yeast Saccharomyces cerevisiae
Rong L; Klein HL
1993 Jan 15;268(2):1252-1259, Journal of biological chemistry
— id: 6501, year: 1993, vol: 268, page: 1252, stat: Journal Article,

Analysis of mitotic and meiotic defects in Saccharomyces cerevisiae SRS2 DNA helicase mutants
Palladino F; Klein HL
1992 Sep;132(1):23-37, Genetics
— id: 13469, year: 1992, vol: 132, page: 23, stat: Journal Article,

The hyper-gene conversion hpr5-1 mutation of Saccharomyces cerevisiae is an allele of the SRS2/RADH gene
Rong L; Palladino F; Aguilera A; Klein HL
1991 Jan;127(1):75-85, Genetics
— id: 14195, year: 1991, vol: 127, page: 75, stat: Journal Article,

HPR1, a novel yeast gene that prevents intrachromosomal excision recombination, shows carboxy-terminal homology to the Saccharomyces cerevisiae TOP1 gene
Aguilera A; Klein HL
1990 Apr;10(4):1439-1451, Molecular & cellular biology
— id: 17418, year: 1990, vol: 10, page: 1439, stat: Journal Article,

Yeast alpha-factor and somatostatin enhance binding of [3H]estradiol to proteins in rat pancreas and Saccharomyces cerevisiae
Grossman, A; Klein, H; Becker, J M; Naider, F
1986 Sep;25(3):299-304, Journal of steroid biochemistry
— id: 99130, year: 1986, vol: 25, page: 299, stat: Journal Article,

Clozapine, chlorpromazine, and placebo in newly hospitalized, acutely schizophrenic patients: a controlled, double-blind comparison
Shopsin, B; Klein, H; Aaronsom, M; Collora, M
1979 Jun;36(6):657-664, Archives of general psychiatry
— id: 104966, year: 1979, vol: 36, page: 657, stat: Journal Article,

Clozapine: double-blind control trial in the treatment of acute schizophrenia [proceedings]
Shopsin, B; Klein, H; Aronson, M
1978 Apr;14(2):12-15, Psychopharmacology bulletin
— id: 104965, year: 1978, vol: 14, page: 12, stat: Journal Article,

Penfluridol: an open phase III study in acute newly admitted hospitalized schizophrenic patients
Shopsin, B; Klein, H; Gerbino, L; Selzer, G
1977 Dec 19;55(2):157-164, Psychopharmacology
— id: 104967, year: 1977, vol: 55, page: 157, stat: Journal Article,

High-dose penfluridol (SEMAP) in acute hospitalized schizophrenic patients
Shopsin, B; Klein, H; Selzer, G
1977 Jul;13(3):24-26, Psychopharmacology bulletin
— id: 105015, year: 1977, vol: 13, page: 24, stat: Journal Article,