Hannah L Klein

Biosketch / Results /

Hannah Klein

Professor, Department of Biochemistry and Molecular Pharmacology;Professor, Department of Medicine;Professor, Department of Pathology
Biochemistry and Molecular Pharmacology

Contact Info

Address
522 First Avenue
New York, NY 10016

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


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

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

Ribonucleotides in DNA: hidden in plain sight
Jinks-Robertson, Sue; Klein, Hannah L
2015-03-09; 1545-9985,Nature structural & molecular biology - id: 1481442, year: 2015 Journal Article

How the misincorporation of ribonucleotides into genomic DNA can be both harmful and helpful to cells
Potenski, Catherine J; Klein, Hannah L
2014-09-22; 0305-1048,Nucleic acids research - id: 1209412, year: 2014 Journal Article

Avoidance of ribonucleotide-induced mutations by RNase H2 and Srs2-Exo1 mechanisms
Potenski, Catherine J; Niu, Hengyao; Sung, Patrick; Klein, Hannah L
2014-08-08; 0028-0836,Nature - id: 1102852, year: 2014 Journal Article; Research Support, N.I.H., Extramural

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
2014-01-20; 1932-6203,PLoS one - id: 741022, year: 2013 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
2013-05-23; 1568-7856,DNA repair (Amsterdam) - id: 348812, year: 2013 Journal Article