Abstract
DNA damage response (DDR) serves as an integrated cellular network to detect cellular stress and react by activating pathways responsible for halting cell cycle progression, stimulating DNA damage repair, and initiating apoptosis. Efficient DDR protects cells from genomic instability while defective DDR can allow DNA lesions to go unrepaired, causing permanent mutations that will affect future generations of cells and possibly cause disease conditions such as cancer. Therefore, DDR mechanisms must be tightly regulated in order to ensure organismal health and viability. One major way of DDR regulation is ubiquitination, which has been long known to control DDR protein localization, activity, and stability. The reversal of this process, deubiquitination, has more recently come to the forefront of DDR research as an important new angle in ubiquitin-mediated regulation of DDR. As such, deubiquitinases have emerged as key factors in DDR. Importantly, deubiquitinases are attractive small-molecule drug targets due to their well-defined catalytic residues that provide a promising avenue for developing new cancer therapeutics. This review focuses on the emerging roles of deubiquitinases in various DNA repair pathways.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 89-98 |
| Number of pages | 10 |
| Journal | DNA Repair |
| Volume | 76 |
| DOIs | |
| State | Published - Apr 1 2019 |
Fingerprint
Keywords
- Deubiquitination
- DNA damage response
- DNA repair
- Post-transcriptional modification
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology
Cite this
Role of deubiquitinases in DNA damage response. / Le, John; Perez, Eric; Nemzow, Leah; Gong, Feng.
In: DNA Repair, Vol. 76, 01.04.2019, p. 89-98.Research output: Contribution to journal › Review article
}
TY - JOUR
T1 - Role of deubiquitinases in DNA damage response
AU - Le, John
AU - Perez, Eric
AU - Nemzow, Leah
AU - Gong, Feng
PY - 2019/4/1
Y1 - 2019/4/1
N2 - DNA damage response (DDR) serves as an integrated cellular network to detect cellular stress and react by activating pathways responsible for halting cell cycle progression, stimulating DNA damage repair, and initiating apoptosis. Efficient DDR protects cells from genomic instability while defective DDR can allow DNA lesions to go unrepaired, causing permanent mutations that will affect future generations of cells and possibly cause disease conditions such as cancer. Therefore, DDR mechanisms must be tightly regulated in order to ensure organismal health and viability. One major way of DDR regulation is ubiquitination, which has been long known to control DDR protein localization, activity, and stability. The reversal of this process, deubiquitination, has more recently come to the forefront of DDR research as an important new angle in ubiquitin-mediated regulation of DDR. As such, deubiquitinases have emerged as key factors in DDR. Importantly, deubiquitinases are attractive small-molecule drug targets due to their well-defined catalytic residues that provide a promising avenue for developing new cancer therapeutics. This review focuses on the emerging roles of deubiquitinases in various DNA repair pathways.
AB - DNA damage response (DDR) serves as an integrated cellular network to detect cellular stress and react by activating pathways responsible for halting cell cycle progression, stimulating DNA damage repair, and initiating apoptosis. Efficient DDR protects cells from genomic instability while defective DDR can allow DNA lesions to go unrepaired, causing permanent mutations that will affect future generations of cells and possibly cause disease conditions such as cancer. Therefore, DDR mechanisms must be tightly regulated in order to ensure organismal health and viability. One major way of DDR regulation is ubiquitination, which has been long known to control DDR protein localization, activity, and stability. The reversal of this process, deubiquitination, has more recently come to the forefront of DDR research as an important new angle in ubiquitin-mediated regulation of DDR. As such, deubiquitinases have emerged as key factors in DDR. Importantly, deubiquitinases are attractive small-molecule drug targets due to their well-defined catalytic residues that provide a promising avenue for developing new cancer therapeutics. This review focuses on the emerging roles of deubiquitinases in various DNA repair pathways.
KW - Deubiquitination
KW - DNA damage response
KW - DNA repair
KW - Post-transcriptional modification
UR - http://www.scopus.com/inward/record.url?scp=85062243151&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85062243151&partnerID=8YFLogxK
U2 - 10.1016/j.dnarep.2019.02.011
DO - 10.1016/j.dnarep.2019.02.011
M3 - Review article
C2 - 30831436
AN - SCOPUS:85062243151
VL - 76
SP - 89
EP - 98
JO - DNA Repair
JF - DNA Repair
SN - 1568-7864
ER -