The ATM and Rad3-related (ATR) serine/threonine kinase mediated signaling responds to several kinds of DNA damage, of which single-stranded DNA (ssDNA) exerts a key role. ssDNAs are induced by stressed replication forks. ATR acting on its substrates prevents the cell from erroneous mitotic entry, plays a key role in interstrand cross link (ICL) repair pathway and also exerts important regulatory roles in homologous recombination pathway of double-strand break repair.