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Guler, G.D.* ; Liu, H.* ; Vaithiyalingam, S.* ; Arnett, D.R.* ; Kremmer, E. ; Chazin, W.J.* ; Fanning, E.*

Human DNA helicase B (HDHB) binds to replication protein A and facilitates cellular recovery from replication stress.

J. Biol. Chem. 287, 6469-6481 (2012)
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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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Single-strandes-DNA; Dependent adenosine-triophosphatase; Polymerase alpha-primase; Mouse FM3A cells; Homologous; Recombination; Saccharomyces-cerevisiae; Genome integrity; Damage response; Terminal domain; T-antigen
Sprache
Veröffentlichungsjahr 2012
HGF-Berichtsjahr 2012
ISSN (print) / ISBN 0021-9258
e-ISSN 1083-351X
Zeitschrift Journal of Biological Chemistry, The
Quellenangaben Band: 287, Heft: 9, Seiten: 6469-6481 Artikelnummer: , Supplement: ,
Verlag American Society for Biochemistry and Molecular Biology
Begutachtungsstatus Peer reviewed
Institut(e) Institute of Molecular Immunology (IMI)
POF Topic(s) 30504 - Mechanisms of Genetic and Environmental Influences on Health and Disease
Forschungsfeld(er) Immune Response and Infection
PSP-Element(e) G-501793-001
PubMed ID 22194613
DOI 10.1074/jbc.M111.324582
WOS ID WOS:000300791800036
Scopus ID 84863181782
Erfassungsdatum 2012-03-28
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