Hannah L. Klein, PhD

While damage to DNA occurs frequently, it is increased in many tumor cells. Therefore, identifying pathways involved in genome maintenance is important for understanding how DNA damage can arise, its consequences, and how it can be prevented. We have two areas of investigation through which we study DNA repair pathways and how the repair of DNA damage is regulated.

We focus mainly on the regulation of DNA motor proteins. These proteins move along the DNA duplex and remove molecules that form obstacles to sensing DNA damage and repairing it through homologous recombination (HR). We have found that modification of these motor proteins through phosphorylation is required for regulating their action and limiting the occurrence of HR to the right situation. Too much HR, or too little, can destabilize the genome. Therefore, regulation of these key proteins is essential for maintaining both the right balance of HR and genome stability.

The second area of our research centers around the occurrence of aberrant replication intermediates in DNA. Although DNA is composed primarily of deoxyribonucleotide residues, with significant frequency ribonucleotide residues are misincorporated into DNA instead. An enzyme called RNase H2 recognizes and removes ribonucleotides from DNA, but when this process is defective DNA damage increases 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 we continue to study the mechanisms by which they maintain the genome.