How do cells deal with DNA damage during replication?

Cells respond to DNA damage through the process known as DNA damage response (DDR). The DDR involves a network of proteins that detect various types of DNA damage, including single-strand breaks, double-strand breaks, and base lesions. These proteins recognize DNA damage and initiate signaling cascades to activate the DDR pathway. When DNA damage is detected, checkpoint proteins halt the cell cycle to allow time for DNA repair before DNA replication or cell division proceeds. This pause in the cell cycle prevents the continuation of damaged DNA to daughter cells. The DDR also involves systems for repairing DSBs, such as homologous recombination (HR) and non-homologous end joining (NHEJ). HR uses a homologous DNA template, typically the sister chromatid, to accurately repair DSBs. NHEJ directly joins broken DNA ends together, often resulting in small insertions or deletions at the repair site. There is also base-excision-repair (BER), which is a DNA repair pathway that corrects small, non-helix-distorting lesions. Additionally, MMR repairs errors such as base-base mismatches and small insertion/deletion loops (indels). Nucleotide excision repair (NER) functions to remove bulky DNA lesions induced by UV irradiation.