{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Xia J"],"funding":["Integrated Microscopy Core","NICHD NIH HHS","CPRIT","NCRR NIH HHS","NIAID NIH HHS","HSRD VA","NIH","American Cancer Society","Dan L. Duncan Comprehensive Cancer Center","NIDDK NIH HHS","NCI NIH HHS","W.M. Keck Foundation","NIGMS NIH HHS","NIH HHS","BCM Cytometry and Cell Sorting Core","John S. Dunn Gulf Coast Consortium for Chemical Genomics"],"pagination":["127-143.e24"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC6344048"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["176(1-2)"],"pubmed_abstract":["DNA damage provokes mutations and cancer and results from external carcinogens or endogenous cellular processes. However, the intrinsic instigators of endogenous DNA damage are poorly understood. Here, we identify proteins that promote endogenous DNA damage when overproduced: the DNA \"damage-up\" proteins (DDPs). We discover a large network of DDPs in Escherichia coli and deconvolute them into six function clusters, demonstrating DDP mechanisms in three: reactive oxygen increase by transmembrane transporters, chromosome loss by replisome binding, and replication stalling by transcription factors. Their 284 human homologs are over-represented among known cancer drivers, and their RNAs in tumors predict heavy mutagenesis and a poor prognosis. Half of the tested human homologs promote DNA dama"],"journal":["Cell"],"pubmed_title":["Bacteria-to-Human Protein Networks Reveal Origins of Endogenous DNA Damage."],"pmcid":["PMC6344048"],"funding_grant_id":["RP140462","DP1 CA174424","CA125123","R01 GM088653","R01 CA175486","T32-GM008231","R1116","P30 AI036211","T32 GM008231","HD007495","RP170005","P30-AI036211","GM102679","132206-PF-18-035-01-DMC","R01 GM102679","R01 CA198279","U01 CA168394","P30 CA125123","DP1-CA174424","U01-CA168394","RP150578","R01 CA201268","DP2 OD008371","IIR 18-035","CA175486","P30 HD007495","GM088653","P30-CA125123","CA201268","RP170295","GM106373","U54 HD007495","U24 CA209851","S10-RR024574","P30 DK056338","DK56338","DP20-OD008371","S10 RR024574","CA198279","RP160283","T32 HD007495","GM089636","RP140553","R01 GM089636","P30 CA016672","R35 GM122598","R01 GM106373","R35-GM122598","U01 CA217842"],"pubmed_authors":["Hastings PJ","Jalali A","Rosenberg SM","Mancini MA","Nehring RB","Siegele DA","Lentzsch AM","Herman C","Szafran AT","Mei Q","Powell RT","LaBonte SA","Queitsch C","Xia J","Zhai Y","Liang H","Miller KM","Wang Y","Perez M","Matadamas Guzman ML","Hu JC","Coarfa C","Fitzgerald DM","Hilsenbeck SG","Chiu LY","Hu CW","Scott KL","Pribis JP","Richters M","Gibson JL","Bates D","Frisch RL","Joshi MC","Bravo Nunez MA"],"additional_accession":[]},"is_claimable":false,"name":"Bacteria-to-Human Protein Networks Reveal Origins of Endogenous DNA Damage.","description":"DNA damage provokes mutations and cancer and results from external carcinogens or endogenous cellular processes. However, the intrinsic instigators of endogenous DNA damage are poorly understood. Here, we identify proteins that promote endogenous DNA damage when overproduced: the DNA \"damage-up\" proteins (DDPs). We discover a large network of DDPs in Escherichia coli and deconvolute them into six function clusters, demonstrating DDP mechanisms in three: reactive oxygen increase by transmembrane transporters, chromosome loss by replisome binding, and replication stalling by transcription factors. Their 284 human homologs are over-represented among known cancer drivers, and their RNAs in tumors predict heavy mutagenesis and a poor prognosis. Half of the tested human homologs promote DNA dama","dates":{"release":"2019-01-01T00:00:00Z","publication":"2019 Jan","modification":"2026-04-14T19:35:27.176Z","creation":"2020-05-22T07:35:28Z"},"accession":"S-EPMC6344048","cross_references":{"pubmed":["30633903"],"doi":["10.1016/j.cell.2018.12.008"]}}