What are DDR proteins?
Abstract. Genome integrity is constantly monitored by sophisticated cellular networks, collectively termed the DNA damage response (DDR). A common feature of DDR proteins is their mobilization in response to genotoxic stress.
What is DDR gene?
Background: The DDR pathway is important in tumor biology, allowing cancer cells a mechanism to resist damage by chemotherapy and radiotherapy. BRCA1/2 are the most well described genes in the pathway, but several others (ATM, ATR, PALB2, etc.) are involved with DDR and are mutated in many cancers.
What is DDR pathway?
DNA damage response (DDR) signaling pathway. Sensors detect DNA damage and activate a cascade of signal transducers, which results in activation of DDR effectors which carry out the appropriate response, such as cell cycle arrest and DNA repair, or apoptosis. DNA can be damaged in several ways.
What is an ATR inhibitor?
An orally bioavailable inhibitor of ataxia telangiectasia and Rad3 related (ATR) kinase, with potential antineoplastic activity.
How is Chk1 activated?
It is well recognized that Chk1 is activated upon phosphorylation at two conserved sites, serine-317 and serine-345 [28, 46, 72]. Although phosphorylation at these two sites is indispensable for the function of Chk1, it remains elusive as to how exactly the phosphorylation activates Chk1 [45].
How is Cdc25 activated?
Cdc25 activates cyclin dependent kinases by removing phosphate from residues in the Cdk active site. In turn, the phosphorylation by M-Cdk (a complex of Cdk1 and cyclin B) activates Cdc25. Together with Wee1, M-Cdk activation is switch-like.
How is ATR inhibited?
AZD6738 is an orally active ATR inhibitor developed by AstraZeneca that has been shown in vitro to inhibit ATR kinase activity at IC50 of 1 nM and CHK1 phosphorylation at IC50 of 74 nM [13]. AZD6738 was shown to suppress both solid and hematological cell lines with an IC50 of less than 1 μM [14, 32, 33].