The Adar Lab
קבוצת אדר
DNA Damage and Repair Intro
What are DNA damages?
The term "DNA damage" refers to any chemical alteration to the DNA structure. This can mean breaks in the sugar phosphate backbone (single strand or double strand breaks), or modifications to the bases themselves.
What types of damages do we study?
Helix-distorting base-damages
Our lab specializes in studying DNA base-damages that distort the helical structure of DNA, and are a strong obstacle to both RNA and DNA polymerases. We work with human cell line models, where these damages are repaired by nucleotide excision repair.
Why do we study DNA damages and DNA repair?
The integrity of the genome is constantly challenged by both internal and external damaging agents. Damages in DNA that block transcription and replication, can lead to cell death. Inaccurate repair of these damages results in the formation of mutations, and enhances the risk for genetic diseases and cancer development.
Nucleotide Excision Repair (NER)
In human cells, helix-distorting DNA damage is removed primarily by a mechanism called Nucleotide Excision Repair (NER). In NER, damage recognition can occur either during global genomic 'surveillance' or via transcription-coupled repair by an elongating RNA polymerase that is blocked by the damage. Once recognized, repair proteins join nucleases to nick the DNA on both sides of the lesion. A short, single-stranded DNA oligonucleotide containing the damage is released. The gap in the genome is filled in by DNA polymerases, resulting in error-free repair. Thus, NER plays a crucial role in maintaining genomic integrity and protecting the cell against mutations linked to cancer and other diseases.
