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PARP1 and PARP2 stabilise replication forks at base excision repair intermediates through Fbh1-dependent Rad51 regulation
by
Piberger, Ann Liza
, Olsen, Anna L.
, Stewart, Grant S.
, McHugh, Peter J.
, Higgs, Martin R.
, Petermann, Eva
, Lakin, Nicholas D.
, Ronson, George E.
in
13
/ 13/106
/ 13/95
/ 14
/ 14/63
/ 45
/ 631/337/1427/1429
/ 631/337/1427/2566
/ 82/51
/ Base excision repair
/ Cell Line
/ Damage prevention
/ Damage tolerance
/ Deoxyribonucleic acid
/ DNA
/ DNA biosynthesis
/ DNA Damage
/ DNA Helicases - antagonists & inhibitors
/ DNA Helicases - genetics
/ DNA Helicases - metabolism
/ DNA polymerase
/ DNA Repair
/ DNA Replication
/ DNA-Binding Proteins - antagonists & inhibitors
/ DNA-Binding Proteins - genetics
/ DNA-Binding Proteins - metabolism
/ Homologous Recombination
/ Homology
/ Humanities and Social Sciences
/ Humans
/ Intermediates
/ multidisciplinary
/ Poly (ADP-Ribose) Polymerase-1 - antagonists & inhibitors
/ Poly (ADP-Ribose) Polymerase-1 - genetics
/ Poly (ADP-Ribose) Polymerase-1 - metabolism
/ Poly(ADP-ribose) polymerase
/ Poly(ADP-ribose) Polymerases - genetics
/ Poly(ADP-ribose) Polymerases - metabolism
/ Protein Stability
/ Rad51 Recombinase - metabolism
/ Repair
/ Replication
/ Replication forks
/ RNA, Small Interfering - genetics
/ S Phase
/ Science
/ Science (multidisciplinary)
2018
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PARP1 and PARP2 stabilise replication forks at base excision repair intermediates through Fbh1-dependent Rad51 regulation
by
Piberger, Ann Liza
, Olsen, Anna L.
, Stewart, Grant S.
, McHugh, Peter J.
, Higgs, Martin R.
, Petermann, Eva
, Lakin, Nicholas D.
, Ronson, George E.
in
13
/ 13/106
/ 13/95
/ 14
/ 14/63
/ 45
/ 631/337/1427/1429
/ 631/337/1427/2566
/ 82/51
/ Base excision repair
/ Cell Line
/ Damage prevention
/ Damage tolerance
/ Deoxyribonucleic acid
/ DNA
/ DNA biosynthesis
/ DNA Damage
/ DNA Helicases - antagonists & inhibitors
/ DNA Helicases - genetics
/ DNA Helicases - metabolism
/ DNA polymerase
/ DNA Repair
/ DNA Replication
/ DNA-Binding Proteins - antagonists & inhibitors
/ DNA-Binding Proteins - genetics
/ DNA-Binding Proteins - metabolism
/ Homologous Recombination
/ Homology
/ Humanities and Social Sciences
/ Humans
/ Intermediates
/ multidisciplinary
/ Poly (ADP-Ribose) Polymerase-1 - antagonists & inhibitors
/ Poly (ADP-Ribose) Polymerase-1 - genetics
/ Poly (ADP-Ribose) Polymerase-1 - metabolism
/ Poly(ADP-ribose) polymerase
/ Poly(ADP-ribose) Polymerases - genetics
/ Poly(ADP-ribose) Polymerases - metabolism
/ Protein Stability
/ Rad51 Recombinase - metabolism
/ Repair
/ Replication
/ Replication forks
/ RNA, Small Interfering - genetics
/ S Phase
/ Science
/ Science (multidisciplinary)
2018
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PARP1 and PARP2 stabilise replication forks at base excision repair intermediates through Fbh1-dependent Rad51 regulation
by
Piberger, Ann Liza
, Olsen, Anna L.
, Stewart, Grant S.
, McHugh, Peter J.
, Higgs, Martin R.
, Petermann, Eva
, Lakin, Nicholas D.
, Ronson, George E.
in
13
/ 13/106
/ 13/95
/ 14
/ 14/63
/ 45
/ 631/337/1427/1429
/ 631/337/1427/2566
/ 82/51
/ Base excision repair
/ Cell Line
/ Damage prevention
/ Damage tolerance
/ Deoxyribonucleic acid
/ DNA
/ DNA biosynthesis
/ DNA Damage
/ DNA Helicases - antagonists & inhibitors
/ DNA Helicases - genetics
/ DNA Helicases - metabolism
/ DNA polymerase
/ DNA Repair
/ DNA Replication
/ DNA-Binding Proteins - antagonists & inhibitors
/ DNA-Binding Proteins - genetics
/ DNA-Binding Proteins - metabolism
/ Homologous Recombination
/ Homology
/ Humanities and Social Sciences
/ Humans
/ Intermediates
/ multidisciplinary
/ Poly (ADP-Ribose) Polymerase-1 - antagonists & inhibitors
/ Poly (ADP-Ribose) Polymerase-1 - genetics
/ Poly (ADP-Ribose) Polymerase-1 - metabolism
/ Poly(ADP-ribose) polymerase
/ Poly(ADP-ribose) Polymerases - genetics
/ Poly(ADP-ribose) Polymerases - metabolism
/ Protein Stability
/ Rad51 Recombinase - metabolism
/ Repair
/ Replication
/ Replication forks
/ RNA, Small Interfering - genetics
/ S Phase
/ Science
/ Science (multidisciplinary)
2018
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PARP1 and PARP2 stabilise replication forks at base excision repair intermediates through Fbh1-dependent Rad51 regulation
Journal Article
PARP1 and PARP2 stabilise replication forks at base excision repair intermediates through Fbh1-dependent Rad51 regulation
2018
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Overview
PARP1 regulates the repair of DNA single-strand breaks generated directly, or during base excision repair (BER). However, the role of PARP2 in these and other repair mechanisms is unknown. Here, we report a requirement for PARP2 in stabilising replication forks that encounter BER intermediates through Fbh1-dependent regulation of Rad51. Whereas PARP2 is dispensable for tolerance of cells to SSBs or homologous recombination dysfunction, it is redundant with PARP1 in BER. Therefore, combined disruption of PARP1 and PARP2 leads to defective BER, resulting in elevated levels of replication-associated DNA damage owing to an inability to stabilise Rad51 at damaged replication forks and prevent uncontrolled DNA resection. Together, our results demonstrate how PARP1 and PARP2 regulate two independent, but intrinsically linked aspects of DNA base damage tolerance by promoting BER directly, and by stabilising replication forks that encounter BER intermediates.
PARP1 has a well characterised role in DNA break repair and base excision repair, whereas the role of PARP2 is less well understood. Here, the authors show a requirement for PARP2 in stabilising replication forks that encounter base excision repair intermediates.
Publisher
Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
Subject
/ 13/106
/ 13/95
/ 14
/ 14/63
/ 45
/ 82/51
/ DNA
/ DNA Helicases - antagonists & inhibitors
/ DNA-Binding Proteins - antagonists & inhibitors
/ DNA-Binding Proteins - genetics
/ DNA-Binding Proteins - metabolism
/ Homology
/ Humanities and Social Sciences
/ Humans
/ Poly (ADP-Ribose) Polymerase-1 - antagonists & inhibitors
/ Poly (ADP-Ribose) Polymerase-1 - genetics
/ Poly (ADP-Ribose) Polymerase-1 - metabolism
/ Poly(ADP-ribose) Polymerases - genetics
/ Poly(ADP-ribose) Polymerases - metabolism
/ Rad51 Recombinase - metabolism
/ Repair
/ RNA, Small Interfering - genetics
/ S Phase
/ Science
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