Abstract
Poly(ADP-ribose) (PAR) polymerase-1 (PARP-1) acts as a DNA damage sensor. It recognizes DNA damage and facilitates DNA repair by recruiting DNA repair machinery to damage sites. Recent studies reported that PARP-1 also plays an important role in DNA replication by recognizing the unligated Okazaki fragments and controlling the speed of fork elongation. On the other hand, emerging evidence reveals that excessive activation of PARP-1 causes chromatin DNA fragmentation and triggers an intrinsic PARP-1-dependent cell death program designated parthanatos, which can be blocked by genetic deletion or pharmacological inhibition of PARP-1. Therefore, PARP-1 plays an essential role in maintaining genomic stability by either facilitating DNA repair/replication or triggering DNA fragmentation to kill cells. A group of structure-specific nucleases is crucial for executing DNA incision and fragmentation following PARP-1 activation. In this review, we will discuss how PARP-1 coordinates with its associated nucleases to maintain genomic integrity and control the decision of cell life and death.
| Original language | English (US) |
|---|---|
| Article number | 102651 |
| Journal | DNA repair |
| DOIs | |
| State | Published - Jan 1 2019 |
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Keywords
- Cell death
- DNA damage
- DNA replication/repair
- Nuclease
- PARP-1
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology
Cite this
PARP-1 and its associated nucleases in DNA damage response. / Wang, Yijie; Luo, Weibo; Wang, Yingfei.
In: DNA repair, 01.01.2019.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - PARP-1 and its associated nucleases in DNA damage response
AU - Wang, Yijie
AU - Luo, Weibo
AU - Wang, Yingfei
PY - 2019/1/1
Y1 - 2019/1/1
N2 - Poly(ADP-ribose) (PAR) polymerase-1 (PARP-1) acts as a DNA damage sensor. It recognizes DNA damage and facilitates DNA repair by recruiting DNA repair machinery to damage sites. Recent studies reported that PARP-1 also plays an important role in DNA replication by recognizing the unligated Okazaki fragments and controlling the speed of fork elongation. On the other hand, emerging evidence reveals that excessive activation of PARP-1 causes chromatin DNA fragmentation and triggers an intrinsic PARP-1-dependent cell death program designated parthanatos, which can be blocked by genetic deletion or pharmacological inhibition of PARP-1. Therefore, PARP-1 plays an essential role in maintaining genomic stability by either facilitating DNA repair/replication or triggering DNA fragmentation to kill cells. A group of structure-specific nucleases is crucial for executing DNA incision and fragmentation following PARP-1 activation. In this review, we will discuss how PARP-1 coordinates with its associated nucleases to maintain genomic integrity and control the decision of cell life and death.
AB - Poly(ADP-ribose) (PAR) polymerase-1 (PARP-1) acts as a DNA damage sensor. It recognizes DNA damage and facilitates DNA repair by recruiting DNA repair machinery to damage sites. Recent studies reported that PARP-1 also plays an important role in DNA replication by recognizing the unligated Okazaki fragments and controlling the speed of fork elongation. On the other hand, emerging evidence reveals that excessive activation of PARP-1 causes chromatin DNA fragmentation and triggers an intrinsic PARP-1-dependent cell death program designated parthanatos, which can be blocked by genetic deletion or pharmacological inhibition of PARP-1. Therefore, PARP-1 plays an essential role in maintaining genomic stability by either facilitating DNA repair/replication or triggering DNA fragmentation to kill cells. A group of structure-specific nucleases is crucial for executing DNA incision and fragmentation following PARP-1 activation. In this review, we will discuss how PARP-1 coordinates with its associated nucleases to maintain genomic integrity and control the decision of cell life and death.
KW - Cell death
KW - DNA damage
KW - DNA replication/repair
KW - Nuclease
KW - PARP-1
UR - http://www.scopus.com/inward/record.url?scp=85068547677&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85068547677&partnerID=8YFLogxK
U2 - 10.1016/j.dnarep.2019.102651
DO - 10.1016/j.dnarep.2019.102651
M3 - Review article
C2 - 31302005
AN - SCOPUS:85068547677
JO - DNA Repair
JF - DNA Repair
SN - 1568-7864
M1 - 102651
ER -