| Title | Remodeling of Interstrand Crosslink Proximal Replisomes Is Dependent on ATR, FANCM, and FANCD2 |
| Authors | Huang, Jing Zhang, Jing Bellani, Marina A. Pokharel, Durga Gichimu, Julia James, Ryan C. Gali, Himabindu Ling, Chen Yan, Zhijiang Xu, Dongyi Chen, Junjie Meetei, Amom Ruhikanta Li, Lei Wang, Weidong Seidman, Michael M. |
| Affiliation | Hunan Univ, Coll Biol, Inst Chem Biol & Nanomed, State Key Lab Chemo Biosensing & Chemometr, Changsha 410082, Hunan, Peoples R China NIA, Lab Mol Gerontol, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA Boston Univ, Dept Pharmacol & Expt Therapeut & Med, Sch Med, 72 East Concord St,K-712D, Boston, MA 02118 USA Univ Texas MD Anderson Canc Ctr, Dept Expt Radiat Oncol, Houston, TX 77225 USA Cincinnati Childrens Hosp Med Ctr, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA Cincinnati Childrens Hosp Med Ctr, Canc & Blood Dis Inst, Cincinnati, OH 45229 USA NIA, Lab Genet & Genom, NIH, 251 Bayview Blvd, Baltimore, MD 21224 USA Peking Univ, Beijing 100871, Peoples R China Wenzhou Med Univ, Sch Basic Med Sci, Inst DNA Repair Dis, Wenzhou, Peoples R China |
| Issue Date | 2019 |
| Publisher | CELL REPORTS |
| Abstract | Eukaryotic replisomes are driven by the mini chromosome maintenance (MCM [M]) helicase complex, an offset ring locked around the template for leading strand synthesis by CDC45 (C) and GINS (G) proteins. Although the CDC45 MCM GINS (CMG) structure implies that interstrand crosslinks (ICLs) are absolute blocks to replisomes, recent studies indicate that cells can restart DNA synthesis on the side of the ICL distal to the initial encounter. Here, we report that restart requires ATR and is promoted by FANCD2 and phosphorylated FANCM. Following introduction of genomic ICLs and dependent on ATR and FANCD2 but not on the Fanconi anemia core proteins or FAAP24, FANCM binds the replisome complex, with concomitant release of the GINS proteins. In situ analysis of replisomes proximal to ICLs confirms the ATR-dependent release of GINS proteins while CDC45 is retained on the remodeled replisome. The results demonstrate the plasticity of CMG composition in response to replication stress. |
| URI | http://hdl.handle.net/20.500.11897/548384 |
| ISSN | 2211-1247 |
| DOI | 10.1016/j.celrep.2019.04.032 |
| Indexed | SCI(E) EI |
| Appears in Collections: | 待认领 |
