DNA end resection and its role in DNA replication and DSB repair choice in mammalian cells

DNA repair: tying up loose ends Carefully regulated enzymatic processing of the ends of DNA strands is essential for efficient replication and damage repair while also minimizing the risk of genomic instability. Replication and repair depend on a mechanism known as DNA resection, in which enzymes trim back double-stranded DNA ends to leave single-stranded overhangs. Zhenkun Lou and colleagues at the Mayo Clinic in Rochester, USA, have reviewed the various steps involved in the initiation and control of DNA resection. There are multiple different DNA repair processes, and the manner in which resection occurs can determine which of these processes subsequently takes place. The authors note that cancer cells rely heavily on these repair pathways to survive radiotherapy and chemotherapy, and highlight research opportunities that might reveal therapeutically useful vulnerabilities in the resection mechanism. DNA end resection has a key role in double-strand break repair and DNA replication. Defective DNA end resection can cause malfunctions in DNA repair and replication, leading to greater genomic instability. DNA end resection is initiated by MRN-CtIP generating short, 3 '-single-stranded DNA (ssDNA). This newly generated ssDNA is further elongated by multiple nucleases and DNA helicases, such as EXO1, DNA2, and BLM. Effective DNA end resection is essential for error-free homologous recombination DNA repair, the degradation of incorrectly replicated DNA and double-strand break repair choice. Because of its importance in DNA repair, DNA end resection is strictly regulated. Numerous mechanisms have been reported to regulate the initiation, extension, and termination of DNA end resection. Here, we review the general process of DNA end resection and its role in DNA replication and repair pathway choice.