Identification of a novel, widespread, and functionally important PCNA-binding motif

Gilljam, Karin M.; Feyzi, Emadoldin; A., Per; Sousa, Mirta Mittelstedt Leal de; Müller, Rebekka; Vågbø, Cathrine Broberg; Catterall, Tara; Liabakk, Nina Beate; Slupphaug, Geir; Drabløs, Finn; Krokan, Hans E.; Otterlei, Marit

doi:10.1083/jcb.200903138

Cited by 155 publications

(265 citation statements)

References 32 publications

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“…It is, however necessary to stress, that repair of etheno-DNA adducts by AlkB proteins is much less efficient than repair of methylated bases. ABH2 was found in replication foci, and contains a motif to bind PCNA [119]. The function of ABH2 might be to clean the template or alternatively participate in replication regulation.…”

Section: Oxidative Dealkylation By Alkb Enzymesmentioning

confidence: 99%

Damage of DNA and proteins by major lipid peroxidation products in genome stability

Winczura

Zdzalik²,

Tudek

2012

Free Radical Research

107

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"Lipid peroxidation induced damage of DNA and proteins in genome stability" by Winczura et. al.We would like to thank the reviewers for their valuable comments. Enclosed, please find the revised version, which includes answers to all questions raised by the reviewers. We changed the text and table presentation according to reviewers recommendations. All changes are marked in the text in red.Sincerely yours

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Section: Oxidative Dealkylation By Alkb Enzymesmentioning

confidence: 99%

Damage of DNA and proteins by major lipid peroxidation products in genome stability

Winczura

Zdzalik²,

Tudek

2012

Free Radical Research

107

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“…The PCNA interacting motif, or PIP box, was first identified in the CDK inhibitor p21/CIP1 (7). More recently, the APIM motif has been identified as an alternative PCNA-binding sequence (8). In addition to its role in DNA replication, PCNA plays a role in both DNA repair and translesion synthesis across sites of damage.…”

mentioning

confidence: 99%

Proliferating cell nuclear antigen (PCNA)-associated KIAA0101/PAF15 protein is a cell cycle-regulated anaphase-promoting complex/cyclosome substrate

Emanuele

Ciccia

Elia

et al. 2011

Proc. Natl. Acad. Sci. U.S.A.

108

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The anaphase-promoting complex/cyclosome (APC/C) is a cell cycleregulated E3 ubiquitin ligase that controls the degradation of substrate proteins at mitotic exit and throughout the G1 phase. We have identified an APC/C substrate and cell cycle-regulated protein, KIAA0101/PAF15. PAF15 protein levels peak in the G2/M phase of the cell cycle and drop rapidly at mitotic exit in an APC/C-and KEN-box-dependent fashion. PAF15 associates with proliferating cell nuclear antigen (PCNA), and depletion of PAF15 decreases the number of cells in S phase, suggesting a role for it in cell cycle regulation. Following irradiation, PAF15 colocalized with γH2AX foci at sites of DNA damage through its interaction with PCNA. Finally, PAF15 depletion led to an increase in homologous recombinationmediated DNA repair, and overexpression caused sensitivity to UV-induced DNA damage. We conclude that PAF15 is an APC/Cregulated protein involved in both cell cycle progression and the DNA damage response.DNA replication | proteolysis

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“…Peptides with high PCNA binding affinity derived from consensus motifs, containing the PIP box motif 19 (such as the peptides presented here) or alternatively peptides containing the APIM consensus motif, 30 possess the inherent ability to competitively interfere with the PCNA recruitment of replication and repair factors. Covalently coupling these peptides to cell-penetrating peptides shows great potential as an effective route to transport these peptides and inhibit proliferative processes (see also Fig.…”

Section: Discussionmentioning

confidence: 99%

A novel cell permeable DNA replication and repair marker

Herce

Rajan

Lättig-Tünnemann

et al. 2014

Nucleus

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Proliferating Cell Nuclear Antigen (PCNA) is a key protein in DNA replication and repair. The dynamics of replication and repair in live cells is usually studied introducing translational fusions of PCNA. To obviate the need for transfection and bypass the problem of difficult to transfect and/or short lived cells, we have now developed a cell permeable replication and/or repair marker. The design of this marker has three essential molecular components: (1) an optimized artificial PCNA binding peptide; (2) a cell-penetrating peptide, derived from the HIV-1 Trans Activator of Transcription (TAT); (3) an in vivo cleavable linker, linking the two peptides. The resulting construct was taken up by human, hamster and mouse cells within minutes of addition to the media. Inside the cells, the cargo separated from the vector peptide and bound PCNA effectively. Both replication and repair sites could be directly labeled in live cells making it the first in vivo cell permeable peptide marker for these two fundamental cellular processes. Concurrently, we also introduced a quick peptide based PCNA staining method as an alternative to PCNA antibodies for immunofluorescence applications. In summary, we present here a versatile tool to instantaneously label repair and replication processes in fixed and live cells.

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Identification of a novel, widespread, and functionally important PCNA-binding motif

Cited by 155 publications

References 32 publications

Damage of DNA and proteins by major lipid peroxidation products in genome stability

Damage of DNA and proteins by major lipid peroxidation products in genome stability

Proliferating cell nuclear antigen (PCNA)-associated KIAA0101/PAF15 protein is a cell cycle-regulated anaphase-promoting complex/cyclosome substrate

A novel cell permeable DNA replication and repair marker

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