DNA Damage, DNA Repair, and Cancer Mutations

Genome instability is a prominent hallmark of cancer. DNA in all living cells is constantly assaulted by DNA damaging agents. The resulting DNA damage, if left unrepaired, interferes with DNA replication and significantly increases mutations. Investigating how DNA damage arises and how it is repaired in the cell is important for the understanding of cancer mutation mechanisms. Dr. Peng Mao uses next-generation sequencing (NGS) and bioinformatics methods to study where DNA damage is formed in the genome and how DNA repair proteins function in the context of chromatin. He has developed two cutting-edge methods, namely, CPD-seq and NMP-seq, for genome-wide mapping of UV-induced photolesions and alkylating agents-induced small base modifications.

CPD-seq (Mao et al., PNAS, 2016;

Mao et al., Nature Communications, 2018)

With these high-throughput mapping methods, he wants to address three questions important to the mutagenesis mechanism in cancer cells: (1) How do DNA repair proteins function in chromatin to remove DNA damage? (2) How does the transcription machinery, including general transcription factors and histone modification enzymes, impact different DNA repair pathways? (3) How do cancer cells selectively modulate DNA repair pathways to tolerate chemotherapeutic agents? Addressing these questions will not only provide new insights into the fundamental mechanism of DNA repair system, but shed light on new strategies to sensitize drug-resistant tumors by inhibiting specific DNA repair pathways.

Chromatin modulates DNA repair and cancer mutations (Mao et al., DNA Repair, 2019)