TRAIP is a PCNA-binding ubiquitin ligase that protects genome stability after replication stress
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TRAIP is a PCNA-binding ubiquitin ligase that protects genome stability after replication stress. / Hoffmann, Saskia; Smedegaard, Stine; Nakamura, Kyosuke; Mortuza, Gulnahar B; Räschle, Markus; Ibañez de Opakua, Alain; Oka, Yasuyoshi; Feng, Yunpeng; Blanco, Francisco J; Mann, Matthias; Montoya, Guillermo; Groth, Anja; Bekker-Jensen, Simon; Mailand, Niels.
In: The Journal of Cell Biology, Vol. 212, No. 1, 04.01.2016, p. 63-75.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - TRAIP is a PCNA-binding ubiquitin ligase that protects genome stability after replication stress
AU - Hoffmann, Saskia
AU - Smedegaard, Stine
AU - Nakamura, Kyosuke
AU - Mortuza, Gulnahar B
AU - Räschle, Markus
AU - Ibañez de Opakua, Alain
AU - Oka, Yasuyoshi
AU - Feng, Yunpeng
AU - Blanco, Francisco J
AU - Mann, Matthias
AU - Montoya, Guillermo
AU - Groth, Anja
AU - Bekker-Jensen, Simon
AU - Mailand, Niels
N1 - © 2016 Hoffmann et al.
PY - 2016/1/4
Y1 - 2016/1/4
N2 - Cellular genomes are highly vulnerable to perturbations to chromosomal DNA replication. Proliferating cell nuclear antigen (PCNA), the processivity factor for DNA replication, plays a central role as a platform for recruitment of genome surveillance and DNA repair factors to replication forks, allowing cells to mitigate the threats to genome stability posed by replication stress. We identify the E3 ubiquitin ligase TRAIP as a new factor at active and stressed replication forks that directly interacts with PCNA via a conserved PCNA-interacting peptide (PIP) box motif. We show that TRAIP promotes ATR-dependent checkpoint signaling in human cells by facilitating the generation of RPA-bound single-stranded DNA regions upon replication stress in a manner that critically requires its E3 ligase activity and is potentiated by the PIP box. Consequently, loss of TRAIP function leads to enhanced chromosomal instability and decreased cell survival after replication stress. These findings establish TRAIP as a PCNA-binding ubiquitin ligase with an important role in protecting genome integrity after obstacles to DNA replication.
AB - Cellular genomes are highly vulnerable to perturbations to chromosomal DNA replication. Proliferating cell nuclear antigen (PCNA), the processivity factor for DNA replication, plays a central role as a platform for recruitment of genome surveillance and DNA repair factors to replication forks, allowing cells to mitigate the threats to genome stability posed by replication stress. We identify the E3 ubiquitin ligase TRAIP as a new factor at active and stressed replication forks that directly interacts with PCNA via a conserved PCNA-interacting peptide (PIP) box motif. We show that TRAIP promotes ATR-dependent checkpoint signaling in human cells by facilitating the generation of RPA-bound single-stranded DNA regions upon replication stress in a manner that critically requires its E3 ligase activity and is potentiated by the PIP box. Consequently, loss of TRAIP function leads to enhanced chromosomal instability and decreased cell survival after replication stress. These findings establish TRAIP as a PCNA-binding ubiquitin ligase with an important role in protecting genome integrity after obstacles to DNA replication.
U2 - 10.1083/jcb.201506071
DO - 10.1083/jcb.201506071
M3 - Journal article
C2 - 26711499
VL - 212
SP - 63
EP - 75
JO - Journal of Cell Biology
JF - Journal of Cell Biology
SN - 0021-9525
IS - 1
ER -
ID: 152960320