MRE11A: a novel negative regulator of human DNA mismatch repair

Research output: Working paper › Preprint › Research

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MRE11A : a novel negative regulator of human DNA mismatch repair. / Du, Demin; Yang, Yueyan; Wang, Guanxiong; Chen, Liying; Guan, Xiaowei; Rasmussen, Lene Juel; Liu, Dekang.

bioRxiv, 2023.

Research output: Working paper › Preprint › Research

Harvard

Du, D, Yang, Y, Wang, G, Chen, L, Guan, X, Rasmussen, LJ & Liu, D 2023 'MRE11A: a novel negative regulator of human DNA mismatch repair' bioRxiv. https://doi.org/10.1101/2023.03.15.532782

APA

Du, D., Yang, Y., Wang, G., Chen, L., Guan, X., Rasmussen, L. J., & Liu, D. (2023). MRE11A: a novel negative regulator of human DNA mismatch repair. bioRxiv. https://doi.org/10.1101/2023.03.15.532782

Vancouver

Du D, Yang Y, Wang G, Chen L, Guan X, Rasmussen LJ et al. MRE11A: a novel negative regulator of human DNA mismatch repair. bioRxiv. 2023. https://doi.org/10.1101/2023.03.15.532782

Author

Du, Demin ; Yang, Yueyan ; Wang, Guanxiong ; Chen, Liying ; Guan, Xiaowei ; Rasmussen, Lene Juel ; Liu, Dekang. / MRE11A : a novel negative regulator of human DNA mismatch repair. bioRxiv, 2023.

Bibtex

@techreport{e4550aaf3aca4216a36be9037608d42e,
title = "MRE11A: a novel negative regulator of human DNA mismatch repair",
abstract = "DNA mismatch repair (MMR) is a highly conserved pathway that corrects DNA replication errors. Although well characterized, MMR factors remain to be identified. As a 3{\textquoteright}-5{\textquoteright} exonuclease and endonuclease, meiotic recombination 11 homolog A (MRE11A) is implicated in multiple DNA repair pathways. However, the role of MRE11A in MMR is unclear. Here, we show that MRE11A deficiency increased the sensitivity of HeLa cells to N-methyl-N{\textquoteright} nitro-N nitrosoguanidine (MNNG) treatment, implying a potential role of MRE11 in MMR. Moreover, we found MRE11A was largely recruited to chromatin and negatively regulated the DNA damage signals within the first cell cycle after MNNG treatment. We also showed that knockdown of MRE11A increased, while overexpressing MRE11A decreased, MMR activity in HeLa cells, suggesting that MRE11A negatively regulates MMR activity. Furthermore, we show that the recruitment of MRE11A to chromatin requires MLH1 and that MRE11A competes with PMS2 for binding to MLH1. This decreases PMS2 levels in whole cell and on chromatin, and consequently comprises MMR activity. Collectively, our findings reveal that MRE11A is a negative regulator of human MMR.",
author = "Demin Du and Yueyan Yang and Guanxiong Wang and Liying Chen and Xiaowei Guan and Rasmussen, {Lene Juel} and Dekang Liu",
year = "2023",
doi = "10.1101/2023.03.15.532782",
language = "English",
publisher = "bioRxiv",
type = "WorkingPaper",
institution = "bioRxiv",

}

RIS

TY - UNPB

T1 - MRE11A

T2 - a novel negative regulator of human DNA mismatch repair

AU - Du, Demin

AU - Yang, Yueyan

AU - Wang, Guanxiong

AU - Chen, Liying

AU - Guan, Xiaowei

AU - Rasmussen, Lene Juel

AU - Liu, Dekang

PY - 2023

Y1 - 2023

N2 - DNA mismatch repair (MMR) is a highly conserved pathway that corrects DNA replication errors. Although well characterized, MMR factors remain to be identified. As a 3’-5’ exonuclease and endonuclease, meiotic recombination 11 homolog A (MRE11A) is implicated in multiple DNA repair pathways. However, the role of MRE11A in MMR is unclear. Here, we show that MRE11A deficiency increased the sensitivity of HeLa cells to N-methyl-N’ nitro-N nitrosoguanidine (MNNG) treatment, implying a potential role of MRE11 in MMR. Moreover, we found MRE11A was largely recruited to chromatin and negatively regulated the DNA damage signals within the first cell cycle after MNNG treatment. We also showed that knockdown of MRE11A increased, while overexpressing MRE11A decreased, MMR activity in HeLa cells, suggesting that MRE11A negatively regulates MMR activity. Furthermore, we show that the recruitment of MRE11A to chromatin requires MLH1 and that MRE11A competes with PMS2 for binding to MLH1. This decreases PMS2 levels in whole cell and on chromatin, and consequently comprises MMR activity. Collectively, our findings reveal that MRE11A is a negative regulator of human MMR.

AB - DNA mismatch repair (MMR) is a highly conserved pathway that corrects DNA replication errors. Although well characterized, MMR factors remain to be identified. As a 3’-5’ exonuclease and endonuclease, meiotic recombination 11 homolog A (MRE11A) is implicated in multiple DNA repair pathways. However, the role of MRE11A in MMR is unclear. Here, we show that MRE11A deficiency increased the sensitivity of HeLa cells to N-methyl-N’ nitro-N nitrosoguanidine (MNNG) treatment, implying a potential role of MRE11 in MMR. Moreover, we found MRE11A was largely recruited to chromatin and negatively regulated the DNA damage signals within the first cell cycle after MNNG treatment. We also showed that knockdown of MRE11A increased, while overexpressing MRE11A decreased, MMR activity in HeLa cells, suggesting that MRE11A negatively regulates MMR activity. Furthermore, we show that the recruitment of MRE11A to chromatin requires MLH1 and that MRE11A competes with PMS2 for binding to MLH1. This decreases PMS2 levels in whole cell and on chromatin, and consequently comprises MMR activity. Collectively, our findings reveal that MRE11A is a negative regulator of human MMR.

U2 - 10.1101/2023.03.15.532782

DO - 10.1101/2023.03.15.532782

M3 - Preprint

BT - MRE11A

PB - bioRxiv

ER -

ID: 382375134