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

Journal Article · · Nucleic Acids Research
DOI:https://doi.org/10.1093/nar/gkv859· OSTI ID:1257378
 [1];  [2];  [3];  [1];  [2];  [3];  [1];  [4];  [2];  [3];  [4];  [1];  [2];  [5]
  1. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
  2. Yale Univ. School of Medicine, New Haven, CT (United States)
  3. Colorado State Univ., Fort Collins, CO (United States)
  4. Univ. of Oslo (Norway)
  5. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States); Colorado State Univ., Fort Collins, CO (United States)

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. Finally, 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.

Research Organization:
Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE
Grant/Contract Number:
AC02-05CH11231
OSTI ID:
1257378
Journal Information:
Nucleic Acids Research, Vol. 43, Issue 20; ISSN 0305-1048
Publisher:
Oxford University PressCopyright Statement
Country of Publication:
United States
Language:
English
Citation Metrics:
Cited by: 40 works
Citation information provided by
Web of Science

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DNA Repair book January 2016
Roles of NUCKS1 in Diseases: Susceptibility, Potential Biomarker, and Regulatory Mechanisms journal January 2018
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Associations of rs823128, rs1572931, and rs823156 polymorphisms with reduced Parkinson’s disease risks journal September 2017
Proteome-wide solubility and thermal stability profiling reveals distinct regulatory roles for ATP journal December 2018
Mycobacterium tuberculosis arrests host cycle at the G1/S transition to establish long term infection journal May 2017
Nucks1 synergizes with Trp53 to promote radiation lymphomagenesis in mice journal August 2016
A Selection of Important Genes and Their Correlated Behavior in Alzheimer’s Disease journal August 2018
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