TY - JOUR
T1 - Role of Translesion DNA Synthesis in the Metabolism of Replication-associated Nascent Strand Gaps
AU - Khatib, Jude B.
AU - Nicolae, Claudia M.
AU - Moldovan, George Lucian
N1 - Publisher Copyright:
© 2023 Elsevier Ltd
PY - 2024/1/1
Y1 - 2024/1/1
N2 - Translesion DNA synthesis (TLS) is a DNA damage tolerance pathway utilized by cells to overcome lesions encountered throughout DNA replication. During replication stress, cancer cells show increased dependency on TLS proteins for cellular survival and chemoresistance. TLS proteins have been described to be involved in various DNA repair pathways. One of the major emerging roles of TLS is single-stranded DNA (ssDNA) gap-filling, primarily after the repriming activity of PrimPol upon encountering a lesion. Conversely, suppression of ssDNA gap accumulation by TLS is considered to represent a mechanism for cancer cells to evade the toxicity of chemotherapeutic agents, specifically in BRCA-deficient cells. Thus, TLS inhibition is emerging as a potential treatment regimen for DNA repair-deficient tumors.
AB - Translesion DNA synthesis (TLS) is a DNA damage tolerance pathway utilized by cells to overcome lesions encountered throughout DNA replication. During replication stress, cancer cells show increased dependency on TLS proteins for cellular survival and chemoresistance. TLS proteins have been described to be involved in various DNA repair pathways. One of the major emerging roles of TLS is single-stranded DNA (ssDNA) gap-filling, primarily after the repriming activity of PrimPol upon encountering a lesion. Conversely, suppression of ssDNA gap accumulation by TLS is considered to represent a mechanism for cancer cells to evade the toxicity of chemotherapeutic agents, specifically in BRCA-deficient cells. Thus, TLS inhibition is emerging as a potential treatment regimen for DNA repair-deficient tumors.
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U2 - 10.1016/j.jmb.2023.168275
DO - 10.1016/j.jmb.2023.168275
M3 - Review article
C2 - 37714300
AN - SCOPUS:85172014713
SN - 0022-2836
VL - 436
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
IS - 1
M1 - 168275
ER -