DNA Damage-induced Ubiquitylation of RFC2 Subunit of Replication Factor C Complex

Tomida, Junya; Masuda, Yuji; Hiroaki, Hidekazu; Ishikawa, Tomoko; Song, Ihnyoung; Tsurimoto, Toshiki; Tateishi, Seiichiro; Shiomi, Tadahiro; Kamei, Yasuhiro; Kim, Jinhyeong; Kamiya, Kenji; Vaziri, Cyrus; Ohmori, Hitoshi; Todo, Tomoki

doi:10.1074/jbc.m709835200

Cited by 33 publications

(29 citation statements)

References 52 publications

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“…28,29 It has been shown that, in the absence of pRb, negative cell growth genes, including other Rb family members, may be upregulated to compensate for pRb function. [30][31][32] Correlating with this, microarray analysis showed upregulation of Rbl1 (p107), Cdkn1a (p21 Cip1 ) and Cdkn2d (p19 Ink4d ) in the pRb -/-inner ear.…”

Section: Resultsmentioning

confidence: 99%

Overlapping and distinct pRb pathways in the mammalian auditory and vestibular organs

Huang

Sage²,

Tang³

et al. 2011

Cell Cycle

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Section: Resultsmentioning

confidence: 99%

Overlapping and distinct pRb pathways in the mammalian auditory and vestibular organs

Huang

Sage²,

Tang³

et al. 2011

Cell Cycle

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“…C mutations were not impaired in the absence of PCNAK164 modification. These observations suggest that not all specialized DNA polymerases depend on PCNA monoubiquitination specifically, but on other ubiquitinated factors [177,178] such as the heterotrimeric Rad9/Rad1/Hus1 sliding clamp (9-1-1 complex) and replication factor C (which can also be ubiquitinated by the Rad6/Rad18 complex) [179,180] or unidentified ubiquitinated components in the replication machinery. Recent data showing that ubiquitinated PCNA is not the only ubiquitinated target that drives Polg into foci, support this idea [45].…”

Section: Mechanisms Of Pcna Monoubiquitination and Dna Polymerase Swimentioning

confidence: 95%

Y-family DNA polymerases in mammalian cells

Guo

Kosarek-Stancel

Tang

et al. 2009

Cell. Mol. Life Sci.

134

159

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Eukaryotic genomes are replicated with high fidelity to assure the faithful transmission of genetic information from one generation to the next. The accuracy of replication relies heavily on the ability of replicative DNA polymerases to efficiently select correct nucleotides for the polymerization reaction and, using their intrinsic exonuclease activities, to excise mistakenly incorporated nucleotides. Cells also possess a variety of specialized DNA polymerases that, by a process called translesion DNA synthesis (TLS), help overcome replication blocks when unrepaired DNA lesions stall the replication machinery. This review considers the properties of the Y-family (a subset of specialized DNA polymerases) and their roles in modulating spontaneous and genotoxic-induced mutations in mammals. We also review recent insights into the molecular mechanisms that regulate PCNA monoubiquitination and DNA polymerase switching during TLS and discuss the potential of using Y-family DNA polymerases as novel targets for cancer prevention and therapy.

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“…In addition to RPA32, it is possible that other cellular replication proteins are modified during the AAV-induced DDR. Cellular minichromosome maintenance proteins are phosphorylated during DNA damage (17,37,68) while RFC2/RFC4 and PCNA can become ubiquitinated (44,78). It will be interesting to determine how AAV-induced signaling impacts these replication factors and their function during productive AAV replication.…”

Section: Discussionmentioning

confidence: 99%

Adeno-Associated Virus Replication Induces a DNA Damage Response Coordinated by DNA-Dependent Protein Kinase

Schwartz

Carson

Schuberth

et al. 2009

J Virol

140

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The parvovirus adeno-associated virus (AAV) contains a small single-stranded DNA genome with inverted terminal repeats that form hairpin structures. In order to propagate, AAV relies on the cellular replication machinery together with functions supplied by coinfecting helper viruses such as adenovirus (Ad). Here, we examined the host cell response to AAV replication in the context of Ad or Ad helper proteins. We show that AAV and Ad coinfection activates a DNA damage response (DDR) that is distinct from that seen during Ad or AAV infection alone. The DDR was also triggered when AAV replicated in the presence of minimal Ad helper proteins. We detected autophosphorylation of the kinases ataxia telangiectasia mutated (ATM) and DNAdependent protein kinase catalytic subunit (DNA-PKcs) and signaling to downstream targets SMC1, Chk1, Chk2, H2AX, and XRCC4 and multiple sites on RPA32. The Mre11 complex was not required for activation of the DDR to AAV infection. Additionally, we found that DNA-PKcs was the primary mediator of damage signaling in response to AAV replication. Immunofluorescence revealed that some activated damage proteins were found in a pan-nuclear pattern (phosphorylated ATM, SMC1, and H2AX), while others such as DNA-PK components (DNA-PKcs, Ku70, and Ku86) and RPA32 accumulated at AAV replication centers. Although expression of the large viral Rep proteins contributed to some damage signaling, we observed that the full response required replication of the AAV genome. Our results demonstrate that AAV replication in the presence of Ad helper functions elicits a unique damage response controlled by DNA-PK.Replication of viral genomes produces a large amount of extrachromosomal DNA that may be recognized by the cellular DNA damage machinery. This is often accompanied by activation of DNA damage response (DDR) signaling pathways and recruitment of cellular repair proteins to sites of viral replication. Viruses therefore provide good model systems to study the recognition and response to DNA damage (reviewed in reference 48). The Mre11/Rad50/Nbs1 (MRN) complex functions as a sensor of chromosomal DNA double-strand breaks (DSBs) and is involved in activation of damage signaling (reviewed in reference 41). The MRN complex also localizes to DNA DSBs and is found at viral replication compartments during infection with a number of DNA viruses (6,40,47,70,75,77,87,93). The phosphatidylinositol 3-kinase-like kinases (PIKKs) ataxia telangiectasia mutated (ATM), ATM and Rad3-related kinase (ATR), and the catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs) are involved in the signal transduction cascades activated by DNA damage (reviewed in references 43, 51, and 71). These kinases respond to distinct types of damage and regulate DSB repair during different phases of the cell cycle (5), either through nonhomologous end-joining (NHEJ) or homologous recombination pathways (reviewed in references 63, 81, and 86). The DNA-PK holoenzyme is composed of DNA-PKcs and two regulatory subunits, the Ku70 and Ku86 het...

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DNA Damage-induced Ubiquitylation of RFC2 Subunit of Replication Factor C Complex

Cited by 33 publications

References 52 publications

Overlapping and distinct pRb pathways in the mammalian auditory and vestibular organs

Overlapping and distinct pRb pathways in the mammalian auditory and vestibular organs

Y-family DNA polymerases in mammalian cells

Adeno-Associated Virus Replication Induces a DNA Damage Response Coordinated by DNA-Dependent Protein Kinase

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