MND1 and PSMC3IP control PARP inhibitor sensitivity in mitotic cells

Anabel Zelceski; Paola Francica; Lea Lingg; Merve Mutlu; Colin Stok; Martin Liptay; John Alexander; Joseph S Baxter; Rachel Brough; Aditi Gulati; Syed Haider; Maya Raghunandan; Feifei Song; Sandhya Sridhar; Josep V Forment; Mark J O'Connor; Barry R Davies; Marcel A T M van Vugt; Dragomir B Krastev; Stephen J Pettitt; Andrew N J Tutt; Sven Rottenberg; Christopher J Lord

doi:10.1016/j.celrep.2023.112484

MND1 and PSMC3IP control PARP inhibitor sensitivity in mitotic cells

Anabel Zelceski, Paola Francica, Lea Lingg, Merve Mutlu, Colin Stok, Martin Liptay, John Alexander, Joseph S Baxter, Rachel Brough, Aditi Gulati, Syed Haider, Maya Raghunandan, Feifei Song, Sandhya Sridhar, Josep V Forment, Mark J O'Connor, Barry R Davies, Marcel A T M van Vugt, Dragomir B Krastev, Stephen J PettittAndrew N J Tutt, Sven Rottenberg, Christopher J Lord^*

^*Corresponding author voor dit werk

Onderzoeksoutput › Academic › peer review

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The PSMC3IP-MND1 heterodimer promotes meiotic D loop formation before DNA strand exchange. In genome-scale CRISPR-Cas9 mutagenesis and interference screens in mitotic cells, depletion of PSMC3IP or MND1 causes sensitivity to poly (ADP-Ribose) polymerase inhibitors (PARPi) used in cancer treatment. PSMC3IP or MND1 depletion also causes ionizing radiation sensitivity. These effects are independent of PSMC3IP/MND1's role in mitotic alternative lengthening of telomeres. PSMC3IP- or MND1-depleted cells accumulate toxic RAD51 foci in response to DNA damage, show impaired homology-directed DNA repair, and become PARPi sensitive, even in cells lacking both BRCA1 and TP53BP1. Epistasis between PSMC3IP-MND1 and BRCA1/BRCA2 defects suggest that abrogated D loop formation is the cause of PARPi sensitivity. Wild-type PSMC3IP reverses PARPi sensitivity, whereas a PSMC3IP p.Glu201del mutant associated with D loop defects and ovarian dysgenesis does not. These observations suggest that meiotic proteins such as MND1 and PSMC3IP have a greater role in mitotic DNA repair.

Originele taal-2	English
Artikelnummer	112484
Aantal pagina's	27
Tijdschrift	Cell reports
Volume	42
Nummer van het tijdschrift	5
Vroegere onlinedatum	9-mei-2023
DOI's	https://doi.org/10.1016/j.celrep.2023.112484
Status	Published - mei-2023

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10.1016/j.celrep.2023.112484Licentie: CC BY

MND1 and PSMC3IP control PARP inhibitor sensitivity in mitotic cellsFinal publisher's version, 5,26 MBLicentie: CC BY

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Zelceski, A., Francica, P., Lingg, L., Mutlu, M., Stok, C., Liptay, M., Alexander, J., Baxter, J. S., Brough, R., Gulati, A., Haider, S., Raghunandan, M., Song, F., Sridhar, S., Forment, J. V., O'Connor, M. J., Davies, B. R., van Vugt, M. A. T. M., Krastev, D. B., ... Lord, C. J. (2023). MND1 and PSMC3IP control PARP inhibitor sensitivity in mitotic cells. Cell reports, 42(5), Artikel 112484. https://doi.org/10.1016/j.celrep.2023.112484

@article{07b31eba4f044b9d8abcbedaaa4ae964,

title = "MND1 and PSMC3IP control PARP inhibitor sensitivity in mitotic cells",

abstract = "The PSMC3IP-MND1 heterodimer promotes meiotic D loop formation before DNA strand exchange. In genome-scale CRISPR-Cas9 mutagenesis and interference screens in mitotic cells, depletion of PSMC3IP or MND1 causes sensitivity to poly (ADP-Ribose) polymerase inhibitors (PARPi) used in cancer treatment. PSMC3IP or MND1 depletion also causes ionizing radiation sensitivity. These effects are independent of PSMC3IP/MND1's role in mitotic alternative lengthening of telomeres. PSMC3IP- or MND1-depleted cells accumulate toxic RAD51 foci in response to DNA damage, show impaired homology-directed DNA repair, and become PARPi sensitive, even in cells lacking both BRCA1 and TP53BP1. Epistasis between PSMC3IP-MND1 and BRCA1/BRCA2 defects suggest that abrogated D loop formation is the cause of PARPi sensitivity. Wild-type PSMC3IP reverses PARPi sensitivity, whereas a PSMC3IP p.Glu201del mutant associated with D loop defects and ovarian dysgenesis does not. These observations suggest that meiotic proteins such as MND1 and PSMC3IP have a greater role in mitotic DNA repair.",

author = "Anabel Zelceski and Paola Francica and Lea Lingg and Merve Mutlu and Colin Stok and Martin Liptay and John Alexander and Baxter, {Joseph S} and Rachel Brough and Aditi Gulati and Syed Haider and Maya Raghunandan and Feifei Song and Sandhya Sridhar and Forment, {Josep V} and O'Connor, {Mark J} and Davies, {Barry R} and {van Vugt}, {Marcel A T M} and Krastev, {Dragomir B} and Pettitt, {Stephen J} and Tutt, {Andrew N J} and Sven Rottenberg and Lord, {Christopher J}",

year = "2023",

month = may,

doi = "10.1016/j.celrep.2023.112484",

language = "English",

volume = "42",

journal = "Cell reports",

issn = "2211-1247",

publisher = "Cell Press",

number = "5",

}

Zelceski, A, Francica, P, Lingg, L, Mutlu, M, Stok, C, Liptay, M, Alexander, J, Baxter, JS, Brough, R, Gulati, A, Haider, S, Raghunandan, M, Song, F, Sridhar, S, Forment, JV, O'Connor, MJ, Davies, BR, van Vugt, MATM, Krastev, DB, Pettitt, SJ, Tutt, ANJ, Rottenberg, S & Lord, CJ 2023, 'MND1 and PSMC3IP control PARP inhibitor sensitivity in mitotic cells', Cell reports, vol. 42, nr. 5, 112484. https://doi.org/10.1016/j.celrep.2023.112484

TY - JOUR

T1 - MND1 and PSMC3IP control PARP inhibitor sensitivity in mitotic cells

AU - Zelceski, Anabel

AU - Francica, Paola

AU - Lingg, Lea

AU - Mutlu, Merve

AU - Stok, Colin

AU - Liptay, Martin

AU - Alexander, John

AU - Baxter, Joseph S

AU - Brough, Rachel

AU - Gulati, Aditi

AU - Haider, Syed

AU - Raghunandan, Maya

AU - Song, Feifei

AU - Sridhar, Sandhya

AU - Forment, Josep V

AU - O'Connor, Mark J

AU - Davies, Barry R

AU - van Vugt, Marcel A T M

AU - Krastev, Dragomir B

AU - Pettitt, Stephen J

AU - Tutt, Andrew N J

AU - Rottenberg, Sven

AU - Lord, Christopher J

PY - 2023/5

Y1 - 2023/5

N2 - The PSMC3IP-MND1 heterodimer promotes meiotic D loop formation before DNA strand exchange. In genome-scale CRISPR-Cas9 mutagenesis and interference screens in mitotic cells, depletion of PSMC3IP or MND1 causes sensitivity to poly (ADP-Ribose) polymerase inhibitors (PARPi) used in cancer treatment. PSMC3IP or MND1 depletion also causes ionizing radiation sensitivity. These effects are independent of PSMC3IP/MND1's role in mitotic alternative lengthening of telomeres. PSMC3IP- or MND1-depleted cells accumulate toxic RAD51 foci in response to DNA damage, show impaired homology-directed DNA repair, and become PARPi sensitive, even in cells lacking both BRCA1 and TP53BP1. Epistasis between PSMC3IP-MND1 and BRCA1/BRCA2 defects suggest that abrogated D loop formation is the cause of PARPi sensitivity. Wild-type PSMC3IP reverses PARPi sensitivity, whereas a PSMC3IP p.Glu201del mutant associated with D loop defects and ovarian dysgenesis does not. These observations suggest that meiotic proteins such as MND1 and PSMC3IP have a greater role in mitotic DNA repair.

AB - The PSMC3IP-MND1 heterodimer promotes meiotic D loop formation before DNA strand exchange. In genome-scale CRISPR-Cas9 mutagenesis and interference screens in mitotic cells, depletion of PSMC3IP or MND1 causes sensitivity to poly (ADP-Ribose) polymerase inhibitors (PARPi) used in cancer treatment. PSMC3IP or MND1 depletion also causes ionizing radiation sensitivity. These effects are independent of PSMC3IP/MND1's role in mitotic alternative lengthening of telomeres. PSMC3IP- or MND1-depleted cells accumulate toxic RAD51 foci in response to DNA damage, show impaired homology-directed DNA repair, and become PARPi sensitive, even in cells lacking both BRCA1 and TP53BP1. Epistasis between PSMC3IP-MND1 and BRCA1/BRCA2 defects suggest that abrogated D loop formation is the cause of PARPi sensitivity. Wild-type PSMC3IP reverses PARPi sensitivity, whereas a PSMC3IP p.Glu201del mutant associated with D loop defects and ovarian dysgenesis does not. These observations suggest that meiotic proteins such as MND1 and PSMC3IP have a greater role in mitotic DNA repair.

U2 - 10.1016/j.celrep.2023.112484

DO - 10.1016/j.celrep.2023.112484

M3 - Article

C2 - 37163373

SN - 2211-1247

VL - 42

JO - Cell reports

JF - Cell reports

IS - 5

M1 - 112484

ER -

MND1 and PSMC3IP control PARP inhibitor sensitivity in mitotic cells

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