NUCKS1 is a novel RAD51AP1 paralog important for homologous recombination and genome stability

Standard

NUCKS1 is a novel RAD51AP1 paralog important for homologous recombination and genome stability. / Parplys, Ann C; Zhao, Weixing; Sharma, Neelam; Groesser, Torsten; Liang, Fengshan; Maranon, David G; Leung, Stanley G; Grundt, Kirsten; Dray, Eloïse; Idate, Rupa; Østvold, Anne Carine; Schild, David; Sung, Patrick; Wiese, Claudia.

In: NUCLEIC ACIDS RES, Vol. 43, No. 20, 31.08.2015, p. 9817-9834.

Research output: SCORING: Contribution to journalSCORING: Journal articleResearchpeer-review

Harvard

Parplys, AC, Zhao, W, Sharma, N, Groesser, T, Liang, F, Maranon, DG, Leung, SG, Grundt, K, Dray, E, Idate, R, Østvold, AC, Schild, D, Sung, P & Wiese, C 2015, 'NUCKS1 is a novel RAD51AP1 paralog important for homologous recombination and genome stability', NUCLEIC ACIDS RES, vol. 43, no. 20, pp. 9817-9834. https://doi.org/10.1093/nar/gkv859

APA

Parplys, A. C., Zhao, W., Sharma, N., Groesser, T., Liang, F., Maranon, D. G., Leung, S. G., Grundt, K., Dray, E., Idate, R., Østvold, A. C., Schild, D., Sung, P., & Wiese, C. (2015). NUCKS1 is a novel RAD51AP1 paralog important for homologous recombination and genome stability. NUCLEIC ACIDS RES, 43(20), 9817-9834. https://doi.org/10.1093/nar/gkv859

Vancouver

Parplys AC, Zhao W, Sharma N, Groesser T, Liang F, Maranon DG et al. NUCKS1 is a novel RAD51AP1 paralog important for homologous recombination and genome stability. NUCLEIC ACIDS RES. 2015 Aug 31;43(20):9817-9834. https://doi.org/10.1093/nar/gkv859

Bibtex

@article{96e6b8e3b15845518508c02ba9b834a9,
title = "NUCKS1 is a novel RAD51AP1 paralog important for homologous recombination and genome stability",
abstract = "NUCKS1 (nuclear casein kinase and cyclin-dependent kinase substrate 1) is a 27 kD chromosomal, vertebrate-specific protein, for which limited functional data exist. Here, we demonstrate that NUCKS1 shares extensive sequence homology with RAD51AP1 (RAD51 associated protein 1), suggesting that these two proteins are paralogs. Similar to the phenotypic effects of RAD51AP1 knockdown, we find that depletion of NUCKS1 in human cells impairs DNA repair by homologous recombination (HR) and chromosome stability. Depletion of NUCKS1 also results in greatly increased cellular sensitivity to mitomycin C (MMC), and in increased levels of spontaneous and MMC-induced chromatid breaks. NUCKS1 is critical to maintaining wild type HR capacity, and, as observed for a number of proteins involved in the HR pathway, functional loss of NUCKS1 leads to a slow down in DNA replication fork progression with a concomitant increase in the utilization of new replication origins. Interestingly, recombinant NUCKS1 shares the same DNA binding preference as RAD51AP1, but binds to DNA with reduced affinity when compared to RAD51AP1. Our results show that NUCKS1 is a chromatin-associated protein with a role in the DNA damage response and in HR, a DNA repair pathway critical for tumor suppression.",
author = "Parplys, {Ann C} and Weixing Zhao and Neelam Sharma and Torsten Groesser and Fengshan Liang and Maranon, {David G} and Leung, {Stanley G} and Kirsten Grundt and Elo{\"i}se Dray and Rupa Idate and {\O}stvold, {Anne Carine} and David Schild and Patrick Sung and Claudia Wiese",
note = "{\textcopyright} The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.",
year = "2015",
month = aug,
day = "31",
doi = "10.1093/nar/gkv859",
language = "English",
volume = "43",
pages = "9817--9834",
journal = "NUCLEIC ACIDS RES",
issn = "0305-1048",
publisher = "Oxford University Press",
number = "20",

}

RIS

TY - JOUR

T1 - NUCKS1 is a novel RAD51AP1 paralog important for homologous recombination and genome stability

AU - Parplys, Ann C

AU - Zhao, Weixing

AU - Sharma, Neelam

AU - Groesser, Torsten

AU - Liang, Fengshan

AU - Maranon, David G

AU - Leung, Stanley G

AU - Grundt, Kirsten

AU - Dray, Eloïse

AU - Idate, Rupa

AU - Østvold, Anne Carine

AU - Schild, David

AU - Sung, Patrick

AU - Wiese, Claudia

N1 - © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

PY - 2015/8/31

Y1 - 2015/8/31

N2 - NUCKS1 (nuclear casein kinase and cyclin-dependent kinase substrate 1) is a 27 kD chromosomal, vertebrate-specific protein, for which limited functional data exist. Here, we demonstrate that NUCKS1 shares extensive sequence homology with RAD51AP1 (RAD51 associated protein 1), suggesting that these two proteins are paralogs. Similar to the phenotypic effects of RAD51AP1 knockdown, we find that depletion of NUCKS1 in human cells impairs DNA repair by homologous recombination (HR) and chromosome stability. Depletion of NUCKS1 also results in greatly increased cellular sensitivity to mitomycin C (MMC), and in increased levels of spontaneous and MMC-induced chromatid breaks. NUCKS1 is critical to maintaining wild type HR capacity, and, as observed for a number of proteins involved in the HR pathway, functional loss of NUCKS1 leads to a slow down in DNA replication fork progression with a concomitant increase in the utilization of new replication origins. Interestingly, recombinant NUCKS1 shares the same DNA binding preference as RAD51AP1, but binds to DNA with reduced affinity when compared to RAD51AP1. Our results show that NUCKS1 is a chromatin-associated protein with a role in the DNA damage response and in HR, a DNA repair pathway critical for tumor suppression.

AB - NUCKS1 (nuclear casein kinase and cyclin-dependent kinase substrate 1) is a 27 kD chromosomal, vertebrate-specific protein, for which limited functional data exist. Here, we demonstrate that NUCKS1 shares extensive sequence homology with RAD51AP1 (RAD51 associated protein 1), suggesting that these two proteins are paralogs. Similar to the phenotypic effects of RAD51AP1 knockdown, we find that depletion of NUCKS1 in human cells impairs DNA repair by homologous recombination (HR) and chromosome stability. Depletion of NUCKS1 also results in greatly increased cellular sensitivity to mitomycin C (MMC), and in increased levels of spontaneous and MMC-induced chromatid breaks. NUCKS1 is critical to maintaining wild type HR capacity, and, as observed for a number of proteins involved in the HR pathway, functional loss of NUCKS1 leads to a slow down in DNA replication fork progression with a concomitant increase in the utilization of new replication origins. Interestingly, recombinant NUCKS1 shares the same DNA binding preference as RAD51AP1, but binds to DNA with reduced affinity when compared to RAD51AP1. Our results show that NUCKS1 is a chromatin-associated protein with a role in the DNA damage response and in HR, a DNA repair pathway critical for tumor suppression.

U2 - 10.1093/nar/gkv859

DO - 10.1093/nar/gkv859

M3 - SCORING: Journal article

C2 - 26323318

VL - 43

SP - 9817

EP - 9834

JO - NUCLEIC ACIDS RES

JF - NUCLEIC ACIDS RES

SN - 0305-1048

IS - 20

ER -