Detail
Článek
Článek online
FT
Medvik - BMČ
  • Je něco špatně v tomto záznamu ?

Novel PNKP mutations causing defective DNA strand break repair and PARP1 hyperactivity in MCSZ

I. Kalasova, H. Hanzlikova, N. Gupta, Y. Li, J. Altmüller, JJ. Reynolds, GS. Stewart, B. Wollnik, G. Yigit, KW. Caldecott,

. 2019 ; 5 (2) : e320. [pub] 20190325

Jazyk angličtina Země Spojené státy americké

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc19029057

Objective: To address the relationship between novel mutations in polynucleotide 5'-kinase 3'-phosphatase (PNKP), DNA strand break repair, and neurologic disease. Methods: We have employed whole-exome sequencing, Sanger sequencing, and molecular/cellular biology. Results: We describe here a patient with microcephaly with early onset seizures (MCSZ) from the Indian sub-continent harboring 2 novel mutations in PNKP, including a pathogenic mutation in the fork-head associated domain. In addition, we confirm that MCSZ is associated with hyperactivation of the single-strand break sensor protein protein poly (ADP-ribose) polymerase 1 (PARP1) following the induction of abortive topoisomerase I activity, a source of DNA strand breakage associated previously with neurologic disease. Conclusions: These data expand the spectrum of PNKP mutations associated with MCSZ and show that PARP1 hyperactivation at unrepaired topoisomerase-induced DNA breaks is a molecular feature of this disease.

Citace poskytuje Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc19029057
003      
CZ-PrNML
005      
20190916160743.0
007      
ta
008      
190813s2019 xxu f 000 0|eng||
009      
AR
024    7_
$a 10.1212/NXG.0000000000000320 $2 doi
035    __
$a (PubMed)31041400
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxu
100    1_
$a Kalasova, Ilona $u Department of Genome Dynamics (I.K., H.H., K.W.C.), Institute of Molecular Genetics of the Czech Academy of Sciences, Czech Republic; Genome Damage and Stability Centre (H.H., K.W.C.), School of Life Sciences, University of Sussex, Falmer, Brighton, UK; Institute of Human Genetics (Y.L., B.W., G.Y.), University Medical Center Göttingen, Germany; Cologne Center for Genomics (J.A.), University of Cologne, Germany; Institute of Cancer and Genomic Sciences (J.J.R., G.S.S.), College of Medical and Dental Sciences, University of Birmingham, UK; and Division of Genetics (N.G.), Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
245    10
$a Novel PNKP mutations causing defective DNA strand break repair and PARP1 hyperactivity in MCSZ / $c I. Kalasova, H. Hanzlikova, N. Gupta, Y. Li, J. Altmüller, JJ. Reynolds, GS. Stewart, B. Wollnik, G. Yigit, KW. Caldecott,
520    9_
$a Objective: To address the relationship between novel mutations in polynucleotide 5'-kinase 3'-phosphatase (PNKP), DNA strand break repair, and neurologic disease. Methods: We have employed whole-exome sequencing, Sanger sequencing, and molecular/cellular biology. Results: We describe here a patient with microcephaly with early onset seizures (MCSZ) from the Indian sub-continent harboring 2 novel mutations in PNKP, including a pathogenic mutation in the fork-head associated domain. In addition, we confirm that MCSZ is associated with hyperactivation of the single-strand break sensor protein protein poly (ADP-ribose) polymerase 1 (PARP1) following the induction of abortive topoisomerase I activity, a source of DNA strand breakage associated previously with neurologic disease. Conclusions: These data expand the spectrum of PNKP mutations associated with MCSZ and show that PARP1 hyperactivation at unrepaired topoisomerase-induced DNA breaks is a molecular feature of this disease.
655    _2
$a časopisecké články $7 D016428
700    1_
$a Hanzlikova, Hana $u Department of Genome Dynamics (I.K., H.H., K.W.C.), Institute of Molecular Genetics of the Czech Academy of Sciences, Czech Republic; Genome Damage and Stability Centre (H.H., K.W.C.), School of Life Sciences, University of Sussex, Falmer, Brighton, UK; Institute of Human Genetics (Y.L., B.W., G.Y.), University Medical Center Göttingen, Germany; Cologne Center for Genomics (J.A.), University of Cologne, Germany; Institute of Cancer and Genomic Sciences (J.J.R., G.S.S.), College of Medical and Dental Sciences, University of Birmingham, UK; and Division of Genetics (N.G.), Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
700    1_
$a Gupta, Neerja $u Department of Genome Dynamics (I.K., H.H., K.W.C.), Institute of Molecular Genetics of the Czech Academy of Sciences, Czech Republic; Genome Damage and Stability Centre (H.H., K.W.C.), School of Life Sciences, University of Sussex, Falmer, Brighton, UK; Institute of Human Genetics (Y.L., B.W., G.Y.), University Medical Center Göttingen, Germany; Cologne Center for Genomics (J.A.), University of Cologne, Germany; Institute of Cancer and Genomic Sciences (J.J.R., G.S.S.), College of Medical and Dental Sciences, University of Birmingham, UK; and Division of Genetics (N.G.), Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
700    1_
$a Li, Yun $u Department of Genome Dynamics (I.K., H.H., K.W.C.), Institute of Molecular Genetics of the Czech Academy of Sciences, Czech Republic; Genome Damage and Stability Centre (H.H., K.W.C.), School of Life Sciences, University of Sussex, Falmer, Brighton, UK; Institute of Human Genetics (Y.L., B.W., G.Y.), University Medical Center Göttingen, Germany; Cologne Center for Genomics (J.A.), University of Cologne, Germany; Institute of Cancer and Genomic Sciences (J.J.R., G.S.S.), College of Medical and Dental Sciences, University of Birmingham, UK; and Division of Genetics (N.G.), Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
700    1_
$a Altmüller, Janine $u Department of Genome Dynamics (I.K., H.H., K.W.C.), Institute of Molecular Genetics of the Czech Academy of Sciences, Czech Republic; Genome Damage and Stability Centre (H.H., K.W.C.), School of Life Sciences, University of Sussex, Falmer, Brighton, UK; Institute of Human Genetics (Y.L., B.W., G.Y.), University Medical Center Göttingen, Germany; Cologne Center for Genomics (J.A.), University of Cologne, Germany; Institute of Cancer and Genomic Sciences (J.J.R., G.S.S.), College of Medical and Dental Sciences, University of Birmingham, UK; and Division of Genetics (N.G.), Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
700    1_
$a Reynolds, John J $u Department of Genome Dynamics (I.K., H.H., K.W.C.), Institute of Molecular Genetics of the Czech Academy of Sciences, Czech Republic; Genome Damage and Stability Centre (H.H., K.W.C.), School of Life Sciences, University of Sussex, Falmer, Brighton, UK; Institute of Human Genetics (Y.L., B.W., G.Y.), University Medical Center Göttingen, Germany; Cologne Center for Genomics (J.A.), University of Cologne, Germany; Institute of Cancer and Genomic Sciences (J.J.R., G.S.S.), College of Medical and Dental Sciences, University of Birmingham, UK; and Division of Genetics (N.G.), Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
700    1_
$a Stewart, Grant S $u Department of Genome Dynamics (I.K., H.H., K.W.C.), Institute of Molecular Genetics of the Czech Academy of Sciences, Czech Republic; Genome Damage and Stability Centre (H.H., K.W.C.), School of Life Sciences, University of Sussex, Falmer, Brighton, UK; Institute of Human Genetics (Y.L., B.W., G.Y.), University Medical Center Göttingen, Germany; Cologne Center for Genomics (J.A.), University of Cologne, Germany; Institute of Cancer and Genomic Sciences (J.J.R., G.S.S.), College of Medical and Dental Sciences, University of Birmingham, UK; and Division of Genetics (N.G.), Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
700    1_
$a Wollnik, Bernd $u Department of Genome Dynamics (I.K., H.H., K.W.C.), Institute of Molecular Genetics of the Czech Academy of Sciences, Czech Republic; Genome Damage and Stability Centre (H.H., K.W.C.), School of Life Sciences, University of Sussex, Falmer, Brighton, UK; Institute of Human Genetics (Y.L., B.W., G.Y.), University Medical Center Göttingen, Germany; Cologne Center for Genomics (J.A.), University of Cologne, Germany; Institute of Cancer and Genomic Sciences (J.J.R., G.S.S.), College of Medical and Dental Sciences, University of Birmingham, UK; and Division of Genetics (N.G.), Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
700    1_
$a Yigit, Gökhan $u Department of Genome Dynamics (I.K., H.H., K.W.C.), Institute of Molecular Genetics of the Czech Academy of Sciences, Czech Republic; Genome Damage and Stability Centre (H.H., K.W.C.), School of Life Sciences, University of Sussex, Falmer, Brighton, UK; Institute of Human Genetics (Y.L., B.W., G.Y.), University Medical Center Göttingen, Germany; Cologne Center for Genomics (J.A.), University of Cologne, Germany; Institute of Cancer and Genomic Sciences (J.J.R., G.S.S.), College of Medical and Dental Sciences, University of Birmingham, UK; and Division of Genetics (N.G.), Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
700    1_
$a Caldecott, Keith W $u Department of Genome Dynamics (I.K., H.H., K.W.C.), Institute of Molecular Genetics of the Czech Academy of Sciences, Czech Republic; Genome Damage and Stability Centre (H.H., K.W.C.), School of Life Sciences, University of Sussex, Falmer, Brighton, UK; Institute of Human Genetics (Y.L., B.W., G.Y.), University Medical Center Göttingen, Germany; Cologne Center for Genomics (J.A.), University of Cologne, Germany; Institute of Cancer and Genomic Sciences (J.J.R., G.S.S.), College of Medical and Dental Sciences, University of Birmingham, UK; and Division of Genetics (N.G.), Department of Pediatrics, All India Institute of Medical Sciences, New Delhi, India.
773    0_
$w MED00200175 $t Neurology. Genetics $x 2376-7839 $g Roč. 5, č. 2 (2019), s. e320
856    41
$u https://pubmed.ncbi.nlm.nih.gov/31041400 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y a $z 0
990    __
$a 20190813 $b ABA008
991    __
$a 20190916161130 $b ABA008
999    __
$a ind $b bmc $g 1434206 $s 1067517
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2019 $b 5 $c 2 $d e320 $e 20190325 $i 2376-7839 $m Neurology. Genetics $n Neurol Genet $x MED00200175
LZP    __
$a Pubmed-20190813

Najít záznam

Citační ukazatele

Pouze přihlášení uživatelé

Možnosti archivace