DNA polymerase η is a substrate for calpain: a possible mechanism for pol η retention in UV-induced replication foci.

Jo-Ann Nettersheim, Régine Janel-Bintz, Lauriane Kuhn, Agnès M Cordonnier

Journal of cell science 2021 Jul 01

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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. © 2021. Published by The Company of Biologists Ltd.

Citation

Jo-Ann Nettersheim, Régine Janel-Bintz, Lauriane Kuhn, Agnès M Cordonnier. DNA polymerase η is a substrate for calpain: a possible mechanism for pol η retention in UV-induced replication foci. Journal of cell science. 2021 Jul 01;134(13)