library_construction_protocol: We followed the BrdU-IP-based protocol as described (Ryba et al., 2011). 75% ethanol fixed cells were stained with Propidium iodide (Nacalai tesque, 29037), then early- and late-S phase cell population (at least 10,000 cells/fraction) were sorted by a Sony SH800 cell sorter (ultra-purity mode). Extracted DNA was sonicated by a Bioruptor UCD-250 (Sonic Bio). BrdU-incorporated DNA was immunoprecipitated using anti-BrdU antibody (BD Biosciences Pharmingen, #555627). BrdU-immunoprecipitated DNA samples were subject to whole-genome amplification (WGA) with a SeqPlex kit (Sigma, SEQXE). NGS libraries were constructed from early- and late-replicating DNA after WGA with an NGS LTP Library Preparation Kit (KAPA, KK8232) according to the manufacturer's instructions