| Literature DB >> 22194613 |
Gulfem Dilek Guler1, Hanjian Liu, Sivaraja Vaithiyalingam, Diana R Arnett, Elisabeth Kremmer, Walter J Chazin, Ellen Fanning.
Abstract
Maintenance of genomic stability in proliferating cells depends on a network of proteins that coordinate chromosomal replication with DNA damage responses. Human DNA helicase B (HELB or HDHB) has been implicated in chromosomal replication, but its role in this coordinated network remains undefined. Here we report that cellular exposure to UV irradiation, camptothecin, or hydroxyurea induces accumulation of HDHB on chromatin in a dose- and time-dependent manner, preferentially in S phase cells. Replication stress-induced recruitment of HDHB to chromatin is independent of checkpoint signaling but correlates with the level of replication protein A (RPA) recruited to chromatin. We show using purified proteins that HDHB physically interacts with the N-terminal domain of the RPA 70-kDa subunit (RPA70N). NMR spectroscopy and site-directed mutagenesis reveal that HDHB docks on the same RPA70N surface that recruits S phase checkpoint signaling proteins to chromatin. Consistent with this pattern of recruitment, cells depleted of HDHB display reduced recovery from replication stress.Entities:
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Year: 2011 PMID： 22194613 PMCID： PMC3307258 DOI： 10.1074/jbc.M111.324582
Source DB: PubMed Journal: J Biol Chem ISSN： 0021-9258 Impact factor: 5.157