Replication of the Mammalian Genome by Replisomes Specific for Euchromatin and Heterochromatin

• DOI: 10.3389/fcell.2021.729265
• Publication Date: 2021-09-03T21:12:40Z
• Authors: Jing Zhang; Marina A. Bellani; Jing Huang; Ryan C. James; Durga Pokharel; Julia Gichimu; Himabindu Gali; Grant Stewart; Michael M. Seidman
• Keywords: Euchromatin; Replisome; Replication; Heterochromatin protein 1

Replisomes follow a schedule in which replication of DNA euchromatin is early S phase while sequences heterochromatin replicate late. Impediments to replication, referred as stress, can stall forks triggering activation the ATR kinase and downstream pathways. While there substantial literature on local consequences replisome stalling–double strand breaks, reversed forks, or genomic rearrangements–there limited understanding determinants stalling vs. continued progression. Although many proteins are recruited stalled replisomes, current models assume single species “stressed” replisome, independent location. Here we describe our approach visualizing fork encounters with potent block imposed by interstrand crosslink (ICL) discovery an unexpected pathway restart (traverse) past intact ICL. Additionally, found two biochemically distinct replisomes distinguished activity different stages chromatin environment. Each contains that contribute ICL traverse.