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Exo1-mediated resection of DNA double-strand break ends generates 3' single-stranded DNA overhangs required for homology-based DNA repair and activation of the ATR-dependent checkpoint. Despite its critical importance in inducing the overall DNA damage response, the mechanisms and regulation of the Exo1 resection pathway remain incompletely understood. Here, we identify the ring-shaped DNA clamp PCNA as a new factor in the Exo1 resection pathway. Using mammalian cells, Xenopus nuclear extracts and purified proteins, we show that after DNA damage, PCNA loads onto double-strand breaks and promotes Exo1 damage association through direct interaction with Exo1. By tethering Exo1 to the DNA substrate, PCNA confers processivity to Exo1 in resection. This role of PCNA in DNA resection is analogous to its function in DNA replication where PCNA serves as a processivity co-factor for DNA polymerases.
Xiaoqing Chen, and
Sharad C Paudyal, and
Re-I Chin, and
Zhongsheng You
January 2013,
The EMBO journal,
Xiaoqing Chen, and
Sharad C Paudyal, and
Re-I Chin, and
Zhongsheng You
September 2021,
Cell death discovery,
Xiaoqing Chen, and
Sharad C Paudyal, and
Re-I Chin, and
Zhongsheng You
August 2018,
The EMBO journal,
Xiaoqing Chen, and
Sharad C Paudyal, and
Re-I Chin, and
Zhongsheng You
November 2022,
Cell death discovery,
Xiaoqing Chen, and
Sharad C Paudyal, and
Re-I Chin, and
Zhongsheng You
June 2023,
Nucleic acids research,
Xiaoqing Chen, and
Sharad C Paudyal, and
Re-I Chin, and
Zhongsheng You
January 2019,
Molecular & cellular oncology,
Xiaoqing Chen, and
Sharad C Paudyal, and
Re-I Chin, and
Zhongsheng You
June 2017,
The Journal of biological chemistry,
Xiaoqing Chen, and
Sharad C Paudyal, and
Re-I Chin, and
Zhongsheng You
November 2007,
Nature,
Xiaoqing Chen, and
Sharad C Paudyal, and
Re-I Chin, and
Zhongsheng You
March 2016,
Nature cell biology,
Xiaoqing Chen, and
Sharad C Paudyal, and
Re-I Chin, and
Zhongsheng You
April 2014,
Nature communications,
