Abstract
High-fidelity replication of DNA, and its accurate segregation to daughter cells, is critical for maintaining genome stability and suppressing cancer. DNA replication forks are stalled by many DNA lesions, activating checkpoint proteins that stabilize stalled forks. Stalled forks may eventually collapse, producing a broken DNA end. Fork restart is typically mediated by proteins initially identified by their roles in homologous recombination repair of DNA double-strand breaks (DSBs). In recent years, several proteins involved in DSB repair by non-homologous end joining (NHEJ) have been implicated in the replication stress response, including DNA-PKcs, Ku, DNA Ligase IV-XRCC4, Artemis, XLF and Metnase. It is currently unclear whether NHEJ proteins are involved in the replication stress response through indirect (signaling) roles, and/or direct roles involving DNA end joining. Additional complexity in the replication stress response centers around RPA, which undergoes significant post-translational modification after stress, and RAD52, a conserved HR protein whose role in DSB repair may have shifted to another protein in higher eukaryotes, such as BRCA2, but retained its role in fork restart. Most cancer therapeutic strategies create DNA replication stress. Thus, it is imperative to gain a better understanding of replication stress response proteins and pathways to improve cancer therapy.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 4-12 |
| Number of pages | 9 |
| Journal | Journal of Molecular Cell Biology |
| Volume | 3 |
| Issue number | 1 |
| DOIs | |
| State | Published - Feb 16 2011 |
| Externally published | Yes |
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Keywords
- Cancer therapy
- DNA repair
- Genome instability
ASJC Scopus subject areas
- Medicine(all)
- Molecular Biology
- Genetics
- Cell Biology
Cite this
More forks on the road to replication stress recovery. / Allen, Chris; Ashley, Amanda K.; Hromas, Robert A; Nickoloff, Jac A.
In: Journal of Molecular Cell Biology, Vol. 3, No. 1, 16.02.2011, p. 4-12.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - More forks on the road to replication stress recovery
AU - Allen, Chris
AU - Ashley, Amanda K.
AU - Hromas, Robert A
AU - Nickoloff, Jac A.
PY - 2011/2/16
Y1 - 2011/2/16
N2 - High-fidelity replication of DNA, and its accurate segregation to daughter cells, is critical for maintaining genome stability and suppressing cancer. DNA replication forks are stalled by many DNA lesions, activating checkpoint proteins that stabilize stalled forks. Stalled forks may eventually collapse, producing a broken DNA end. Fork restart is typically mediated by proteins initially identified by their roles in homologous recombination repair of DNA double-strand breaks (DSBs). In recent years, several proteins involved in DSB repair by non-homologous end joining (NHEJ) have been implicated in the replication stress response, including DNA-PKcs, Ku, DNA Ligase IV-XRCC4, Artemis, XLF and Metnase. It is currently unclear whether NHEJ proteins are involved in the replication stress response through indirect (signaling) roles, and/or direct roles involving DNA end joining. Additional complexity in the replication stress response centers around RPA, which undergoes significant post-translational modification after stress, and RAD52, a conserved HR protein whose role in DSB repair may have shifted to another protein in higher eukaryotes, such as BRCA2, but retained its role in fork restart. Most cancer therapeutic strategies create DNA replication stress. Thus, it is imperative to gain a better understanding of replication stress response proteins and pathways to improve cancer therapy.
AB - High-fidelity replication of DNA, and its accurate segregation to daughter cells, is critical for maintaining genome stability and suppressing cancer. DNA replication forks are stalled by many DNA lesions, activating checkpoint proteins that stabilize stalled forks. Stalled forks may eventually collapse, producing a broken DNA end. Fork restart is typically mediated by proteins initially identified by their roles in homologous recombination repair of DNA double-strand breaks (DSBs). In recent years, several proteins involved in DSB repair by non-homologous end joining (NHEJ) have been implicated in the replication stress response, including DNA-PKcs, Ku, DNA Ligase IV-XRCC4, Artemis, XLF and Metnase. It is currently unclear whether NHEJ proteins are involved in the replication stress response through indirect (signaling) roles, and/or direct roles involving DNA end joining. Additional complexity in the replication stress response centers around RPA, which undergoes significant post-translational modification after stress, and RAD52, a conserved HR protein whose role in DSB repair may have shifted to another protein in higher eukaryotes, such as BRCA2, but retained its role in fork restart. Most cancer therapeutic strategies create DNA replication stress. Thus, it is imperative to gain a better understanding of replication stress response proteins and pathways to improve cancer therapy.
KW - Cancer therapy
KW - DNA repair
KW - Genome instability
UR - http://www.scopus.com/inward/record.url?scp=79951470434&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79951470434&partnerID=8YFLogxK
U2 - 10.1093/jmcb/mjq049
DO - 10.1093/jmcb/mjq049
M3 - Article
C2 - 21278446
AN - SCOPUS:79951470434
VL - 3
SP - 4
EP - 12
JO - Journal of Molecular Cell Biology
JF - Journal of Molecular Cell Biology
SN - 1674-2788
IS - 1
ER -