DNA damage refers to the permanent alteration of nucleotide sequences during DNA replication,leading to modifications in genetic characteristics.Cells can rectify the majority of such damage through DNA damage repair(...DNA damage refers to the permanent alteration of nucleotide sequences during DNA replication,leading to modifications in genetic characteristics.Cells can rectify the majority of such damage through DNA damage repair(DDR)mechanisms-including base excision repair(BER),nucleotide excision repair(NER),mismatch repair(MMR),homologous recombination(HR),canonical non-homologous end joining(NHEJ),and alternative non-homologous end joining(alt-NHEJ)-thereby maintaining genomic stability.1 Extrachromosomal DNA(ecDNA)refers to circular DNA molecules existing outside chromosomes,which have been demonstrated to play a critical role in tumor progression and evolution.2 EcDNA has been considered a marker of genomic instability,as ecDNA-positive tumors have been found to exhibit elevated DNA replication stress and higher levels of DNA double-strand breaks(DSBs).3 However,the precise relationship between ecDNA and the DDR,as well as the specific mechanisms governing ecDNA replication and maintenance,remains to be elucidated.展开更多
文摘DNA damage refers to the permanent alteration of nucleotide sequences during DNA replication,leading to modifications in genetic characteristics.Cells can rectify the majority of such damage through DNA damage repair(DDR)mechanisms-including base excision repair(BER),nucleotide excision repair(NER),mismatch repair(MMR),homologous recombination(HR),canonical non-homologous end joining(NHEJ),and alternative non-homologous end joining(alt-NHEJ)-thereby maintaining genomic stability.1 Extrachromosomal DNA(ecDNA)refers to circular DNA molecules existing outside chromosomes,which have been demonstrated to play a critical role in tumor progression and evolution.2 EcDNA has been considered a marker of genomic instability,as ecDNA-positive tumors have been found to exhibit elevated DNA replication stress and higher levels of DNA double-strand breaks(DSBs).3 However,the precise relationship between ecDNA and the DDR,as well as the specific mechanisms governing ecDNA replication and maintenance,remains to be elucidated.
