Genome Instability and DNA Damage Pathways
We have two areas of investigation to study DNA damage pathways and how damage repair is regulated. As DNA damage is increased in many tumor cells, identification fo pathways of genome maintenance is important for understanding how damage can arise, the consequences of DNA damage and how it can be prevented. The first area is focused on the regulation of DNA motor proteins. These proteins move along the DNA duplex and remove proteins that are obstacles to sensing and completing homologous recombination (HR) to repair DNA damage. We have found that modification of the motor proteins through phosphorylation is key to regulating their action and limiting HR to act in the right situation. Too much HR or too little HR are both able to destabilize the genome, so regulation of these key proteins is essential to maintain the right balance of HR.
A second area of research centers around the occurrence of aberrant intermediates in DNA. Although DNA is composed primarily of deoxyribonucleotide residues, at a significant frequency ribonucleotide residues are misincorporated into DNA instead. Ribonucleotides in DNA are recognized and removed by an enzyme called RNase H2, but when this process is defective, DNA damage is increased and several genome errors occur, including mutations, chromosome loss and increased HR. We have identified some of the proteins that protect the genome against damage from ribonucleotides in DNA, and are continuing to study the mechanisms by which they maintain the genome.
ACLS Building, 3rd Floor
450 East 29th Street
New York, NY 10016
Professor, Department of Biochemistry and Molecular Pharmacology
Professor, Department of Medicine
Professor, Department of Pathology
Co-Course Director, Current Topics in Genome Integrity
Course Director, Genetics
Vice Chair, Department of Biochemistry and Molecular Pharmacology
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