@article{nettersheim_dna_2021,
title = {DNA polymerase η is a substrate for calpain: a possible mechanism for pol η retention in UV-induced replication foci},
author = {Jo-Ann Nettersheim and Régine Janel-Bintz and Lauriane Kuhn and Agnès M. Cordonnier},
doi = {10.1242/jcs.258637},
issn = {1477-9137},
year = {2021},
date = {2021-07-01},
journal = {Journal of Cell Science},
volume = {134},
number = {13},
pages = {jcs258637},
abstract = {DNA polymerase η (pol η) is specifically required for translesion DNA synthesis across UV-induced DNA lesions. Recruitment of this error-prone DNA polymerase is tightly regulated during replication to avoid mutagenesis and perturbation of fork progression. Here, we report that pol η interacts with the calpain small subunit-1 (CAPNS1) in a yeast two-hybrid screening. This interaction is functional, as demonstrated by the ability of endogenous calpain to mediate calcium-dependent cleavage of pol η in cell-free extracts and in living cells treated with a calcium ionophore. The proteolysis of pol η was found to occur at position 465, leading to a catalytically active truncated protein containing the PCNA-interacting motif PIP1. Unexpectedly, cell treatment with the specific calpain inhibitor calpeptin resulted in a decreased extent of pol η foci after UV irradiation, indicating that calpain positively regulates pol η accumulation in replication foci.},
keywords = {calpain, Calpain protease, CAPNS1, DNA Damage, DNA damage response, DNA polymerase η, DNA Repair, DNA Replication, DNA-Directed DNA Polymerase, PPSE, Replication foci, Translesion DNA synthesis},
pubstate = {published},
tppubtype = {article}
}
DNA polymerase η (pol η) is specifically required for translesion DNA synthesis across UV-induced DNA lesions. Recruitment of this error-prone DNA polymerase is tightly regulated during replication to avoid mutagenesis and perturbation of fork progression. Here, we report that pol η interacts with the calpain small subunit-1 (CAPNS1) in a yeast two-hybrid screening. This interaction is functional, as demonstrated by the ability of endogenous calpain to mediate calcium-dependent cleavage of pol η in cell-free extracts and in living cells treated with a calcium ionophore. The proteolysis of pol η was found to occur at position 465, leading to a catalytically active truncated protein containing the PCNA-interacting motif PIP1. Unexpectedly, cell treatment with the specific calpain inhibitor calpeptin resulted in a decreased extent of pol η foci after UV irradiation, indicating that calpain positively regulates pol η accumulation in replication foci.