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EMBO J
2006 Jun 07;2511:2605-14. doi: 10.1038/sj.emboj.7601123.
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Opposing effects of the UV lesion repair protein XPA and UV bypass polymerase eta on ATR checkpoint signaling.
Bomgarden RD, Lupardus PJ, Soni DV, Yee MC, Ford JM, Cimprich KA.
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An essential component of the ATR (ataxia telangiectasia-mutated and Rad3-related)-activating structure is single-stranded DNA. It has been suggested that nucleotide excision repair (NER) can lead to activation of ATR by generating such a signal, and in yeast, DNA damage processing through the NER pathway is necessary for checkpoint activation during G1. We show here that ultraviolet (UV) radiation-induced ATR signaling is compromised in XPA-deficient human cells during S phase, as shown by defects in ATRIP (ATR-interacting protein) translocation to sites of UV damage, UV-induced phosphorylation of Chk1 and UV-induced replication protein A phosphorylation and chromatin binding. However, ATR signaling was not compromised in XPC-, CSB-, XPF- and XPG-deficient cells. These results indicate that damage processing is not necessary for ATR-mediated S-phase checkpoint activation and that the lesion recognition function of XPA may be sufficient. In contrast, XP-V cells deficient in the UV bypass polymerase eta exhibited enhanced ATR signaling. Taken together, these results suggest that lesion bypass and not lesion repair may raise the level of UV damage that can be tolerated before checkpoint activation, and that XPA plays a critical role in this activation.
Abraham,
Cell cycle checkpoint signaling through the ATM and ATR kinases.
2001, Pubmed
Abraham,
Cell cycle checkpoint signaling through the ATM and ATR kinases.
2001,
Pubmed Adimoolam,
p53 and regulation of DNA damage recognition during nucleotide excision repair.
2003,
Pubmed Bakkenist,
Initiating cellular stress responses.
2004,
Pubmed Ball,
ATRIP binding to replication protein A-single-stranded DNA promotes ATR-ATRIP localization but is dispensable for Chk1 phosphorylation.
2005,
Pubmed Barr,
ATR kinase activity regulates the intranuclear translocation of ATR and RPA following ionizing radiation.
2003,
Pubmed Bassett,
The role of DNA polymerase eta in translesion synthesis past platinum-DNA adducts in human fibroblasts.
2004,
Pubmed Bi,
DNA polymerase kappa is specifically required for recovery from the benzo[a]pyrene-dihydrodiol epoxide (BPDE)-induced S-phase checkpoint.
2005,
Pubmed Binz,
Replication protein A phosphorylation and the cellular response to DNA damage.
2004,
Pubmed Bomgarden,
A novel protein activity mediates DNA binding of an ATR-ATRIP complex.
2004,
Pubmed Brown,
Essential and dispensable roles of ATR in cell cycle arrest and genome maintenance.
2003,
Pubmed Byun,
Functional uncoupling of MCM helicase and DNA polymerase activities activates the ATR-dependent checkpoint.
2005,
Pubmed
,
Xenbase Chen,
Defining the function of xeroderma pigmentosum group F protein in psoralen interstrand cross-link-mediated DNA repair and mutagenesis.
2004,
Pubmed Cliby,
Overexpression of a kinase-inactive ATR protein causes sensitivity to DNA-damaging agents and defects in cell cycle checkpoints.
1998,
Pubmed Cortez,
ATR and ATRIP: partners in checkpoint signaling.
2001,
Pubmed Cortez,
Unwind and slow down: checkpoint activation by helicase and polymerase uncoupling.
2005,
Pubmed Costa,
The eukaryotic nucleotide excision repair pathway.
2003,
Pubmed de Laat,
Molecular mechanism of nucleotide excision repair.
1999,
Pubmed Fitch,
p53 responsive nucleotide excision repair gene products p48 and XPC, but not p53, localize to sites of UV-irradiation-induced DNA damage, in vivo.
2003,
Pubmed Fleck,
Translesion DNA synthesis: little fingers teach tolerance.
2004,
Pubmed Ford,
Role of DNA excision repair gene defects in the etiology of cancer.
1997,
Pubmed Giannattasio,
Physical and functional interactions between nucleotide excision repair and DNA damage checkpoint.
2004,
Pubmed Giannattasio,
DNA decay and limited Rad53 activation after liquid holding of UV-treated nucleotide excision repair deficient S. cerevisiae cells.
2004,
Pubmed Guo,
Requirement for Atr in phosphorylation of Chk1 and cell cycle regulation in response to DNA replication blocks and UV-damaged DNA in Xenopus egg extracts.
2000,
Pubmed
,
Xenbase Hanawalt,
Subpathways of nucleotide excision repair and their regulation.
2002,
Pubmed Hekmat-Nejad,
Xenopus ATR is a replication-dependent chromatin-binding protein required for the DNA replication checkpoint.
,
Pubmed
,
Xenbase Ichikawa,
Decreased UV sensitivity, mismatch repair activity and abnormal cell cycle checkpoints in skin cancer cell lines derived from UVB-irradiated XPA-deficient mice.
2000,
Pubmed Jiang,
Recruitment of DNA damage checkpoint proteins to damage in transcribed and nontranscribed sequences.
2006,
Pubmed Kannouche,
Xeroderma pigmentosum variant and error-prone DNA polymerases.
2003,
Pubmed Kim,
Phosphorylation of Chk1 by ATM- and Rad3-related (ATR) in Xenopus egg extracts requires binding of ATRIP to ATR but not the stable DNA-binding or coiled-coil domains of ATRIP.
2005,
Pubmed
,
Xenbase Klein,
Transformation and immortalization of diploid xeroderma pigmentosum fibroblasts.
1990,
Pubmed Kondo,
Recruitment of Mec1 and Ddc1 checkpoint proteins to double-strand breaks through distinct mechanisms.
2001,
Pubmed Kumagai,
The Xenopus Chk1 protein kinase mediates a caffeine-sensitive pathway of checkpoint control in cell-free extracts.
1998,
Pubmed
,
Xenbase Lee,
Claspin, a Chk1-regulatory protein, monitors DNA replication on chromatin independently of RPA, ATR, and Rad17.
2003,
Pubmed
,
Xenbase Lehmann,
DNA repair-deficient diseases, xeroderma pigmentosum, Cockayne syndrome and trichothiodystrophy.
2003,
Pubmed Lehmann,
Replication of damaged DNA by translesion synthesis in human cells.
2005,
Pubmed Limoli,
UV-induced replication arrest in the xeroderma pigmentosum variant leads to DNA double-strand breaks, gamma -H2AX formation, and Mre11 relocalization.
2002,
Pubmed Lin,
Transcription promotes contraction of CAG repeat tracts in human cells.
2006,
Pubmed Liu,
Chk1 is an essential kinase that is regulated by Atr and required for the G(2)/M DNA damage checkpoint.
2000,
Pubmed Lopes,
Multiple mechanisms control chromosome integrity after replication fork uncoupling and restart at irreparable UV lesions.
2006,
Pubmed Lupardus,
A requirement for replication in activation of the ATR-dependent DNA damage checkpoint.
2002,
Pubmed
,
Xenbase Masutani,
The XPV (xeroderma pigmentosum variant) gene encodes human DNA polymerase eta.
1999,
Pubmed Matsuda,
DNA repair protein XPA binds replication protein A (RPA).
1995,
Pubmed Melo,
Two checkpoint complexes are independently recruited to sites of DNA damage in vivo.
2001,
Pubmed Melo,
A unified view of the DNA-damage checkpoint.
2002,
Pubmed
,
Xenbase Mori,
Simultaneous establishment of monoclonal antibodies specific for either cyclobutane pyrimidine dimer or (6-4)photoproduct from the same mouse immunized with ultraviolet-irradiated DNA.
1991,
Pubmed Murray,
Cell cycle extracts.
1991,
Pubmed Neecke,
Cell cycle progression in the presence of irreparable DNA damage is controlled by a Mec1- and Rad53-dependent checkpoint in budding yeast.
1999,
Pubmed Nelson,
DNA strand breaks: the DNA template alterations that trigger p53-dependent DNA damage response pathways.
1994,
Pubmed O'Connell,
G2 damage checkpoints: what is the turn-on?
2005,
Pubmed O'Connell,
The G2-phase DNA-damage checkpoint.
2000,
Pubmed O'Driscoll,
A splicing mutation affecting expression of ataxia-telangiectasia and Rad3-related protein (ATR) results in Seckel syndrome.
2003,
Pubmed Osborn,
Checking on the fork: the DNA-replication stress-response pathway.
2002,
Pubmed Pacek,
A requirement for MCM7 and Cdc45 in chromosome unwinding during eukaryotic DNA replication.
2004,
Pubmed
,
Xenbase Prakash,
Translesion DNA synthesis in eukaryotes: a one- or two-polymerase affair.
2002,
Pubmed Rouse,
Interfaces between the detection, signaling, and repair of DNA damage.
2002,
Pubmed Stigger,
Functional analysis of human replication protein A in nucleotide excision repair.
1998,
Pubmed Tibbetts,
A role for ATR in the DNA damage-induced phosphorylation of p53.
1999,
Pubmed Tuo,
The cockayne syndrome group B gene product is involved in cellular repair of 8-hydroxyadenine in DNA.
2002,
Pubmed Volker,
Sequential assembly of the nucleotide excision repair factors in vivo.
2001,
Pubmed Ward,
UV-induced ataxia-telangiectasia-mutated and Rad3-related (ATR) activation requires replication stress.
2004,
Pubmed Zachos,
Chk1-deficient tumour cells are viable but exhibit multiple checkpoint and survival defects.
2003,
Pubmed Zachos,
Chk1-dependent S-M checkpoint delay in vertebrate cells is linked to maintenance of viable replication structures.
2005,
Pubmed Zhao,
ATR-mediated checkpoint pathways regulate phosphorylation and activation of human Chk1.
2001,
Pubmed Zhou,
The DNA damage response: putting checkpoints in perspective.
2000,
Pubmed Zou,
Sensing DNA damage through ATRIP recognition of RPA-ssDNA complexes.
2003,
Pubmed Zou,
Regulation of ATR substrate selection by Rad17-dependent loading of Rad9 complexes onto chromatin.
2002,
Pubmed
