TY - JOUR
T1 - A role for DNA polymerase θ in promoting replication through oxidative DNA lesion, thymine glycol, in human cells
AU - Yoon, Jung Hoon
AU - Choudhury, Jayati Roy
AU - Park, Jeseong
AU - Prakash, Satya
AU - Prakash, Louise
PY - 2014
Y1 - 2014
N2 - The biological functions of human DNA polymerase (pol) θ, an A family polymerase, have remained poorly defined. Here we identify a role of polθ in translesion synthesis (TLS) in human cells.Weshow that TLS through the thymine glycol (TG) lesion, the most common oxidation product of thymine, occurs via two alternative pathways, in one of which, polymerases κ and ζ function together and mediate error-free TLS, whereas in the other, polθ functions in an error-prone manner. Human polθ is comprised of an N-terminal ATPase/helicase domain, a large central domain, and a C-terminal polymerase domain; however, we find that only the C-terminal polymerase domain is required for TLS oppositeTGinhumancells. In contrast to TLS mediated by polα and polζ, in which polζ would elongate the chain from the TG:A base pair formed by polθ action, the ability of polθ alone to carry out the nucleotide insertion step, as well as the subsequent extension step that presents a considerable impediment due to displacement of the 5' template base, suggests that the polθ active site can accommodate highly distorting DNA lesions.
AB - The biological functions of human DNA polymerase (pol) θ, an A family polymerase, have remained poorly defined. Here we identify a role of polθ in translesion synthesis (TLS) in human cells.Weshow that TLS through the thymine glycol (TG) lesion, the most common oxidation product of thymine, occurs via two alternative pathways, in one of which, polymerases κ and ζ function together and mediate error-free TLS, whereas in the other, polθ functions in an error-prone manner. Human polθ is comprised of an N-terminal ATPase/helicase domain, a large central domain, and a C-terminal polymerase domain; however, we find that only the C-terminal polymerase domain is required for TLS oppositeTGinhumancells. In contrast to TLS mediated by polα and polζ, in which polζ would elongate the chain from the TG:A base pair formed by polθ action, the ability of polθ alone to carry out the nucleotide insertion step, as well as the subsequent extension step that presents a considerable impediment due to displacement of the 5' template base, suggests that the polθ active site can accommodate highly distorting DNA lesions.
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U2 - 10.1074/jbc.M114.556977
DO - 10.1074/jbc.M114.556977
M3 - Article
C2 - 24648516
AN - SCOPUS:84900386962
SN - 0021-9258
VL - 289
SP - 13177
EP - 13185
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 19
ER -