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Preferential cis–syn thymine dimer bypass by DNA polymerase η occurs with biased fidelity
by
Kunkel, Thomas A.
, Masutani, Chikahide
, Hanaoka, Fumio
, McCulloch, Scott D.
, Kokoska, Robert J.
, Iwai, Shigenori
in
Base Pairing
/ Biological and medical sciences
/ Deoxyribonucleic acid
/ DNA
/ DNA - biosynthesis
/ DNA - chemistry
/ DNA - genetics
/ DNA - metabolism
/ DNA Damage
/ DNA polymerase
/ DNA-Directed DNA Polymerase - metabolism
/ Fundamental and applied biological sciences. Psychology
/ Humanities and Social Sciences
/ Humans
/ Hydrogen Bonding
/ letter
/ Molecular and cellular biology
/ Molecular genetics
/ multidisciplinary
/ Mutagenesis
/ Pyrimidine Dimers - genetics
/ Pyrimidine Dimers - metabolism
/ Replication
/ Science
/ Science (multidisciplinary)
/ Skin cancer
/ Sulfolobus - enzymology
/ thymidine dimers
2004
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Preferential cis–syn thymine dimer bypass by DNA polymerase η occurs with biased fidelity
by
Kunkel, Thomas A.
, Masutani, Chikahide
, Hanaoka, Fumio
, McCulloch, Scott D.
, Kokoska, Robert J.
, Iwai, Shigenori
in
Base Pairing
/ Biological and medical sciences
/ Deoxyribonucleic acid
/ DNA
/ DNA - biosynthesis
/ DNA - chemistry
/ DNA - genetics
/ DNA - metabolism
/ DNA Damage
/ DNA polymerase
/ DNA-Directed DNA Polymerase - metabolism
/ Fundamental and applied biological sciences. Psychology
/ Humanities and Social Sciences
/ Humans
/ Hydrogen Bonding
/ letter
/ Molecular and cellular biology
/ Molecular genetics
/ multidisciplinary
/ Mutagenesis
/ Pyrimidine Dimers - genetics
/ Pyrimidine Dimers - metabolism
/ Replication
/ Science
/ Science (multidisciplinary)
/ Skin cancer
/ Sulfolobus - enzymology
/ thymidine dimers
2004
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Preferential cis–syn thymine dimer bypass by DNA polymerase η occurs with biased fidelity
by
Kunkel, Thomas A.
, Masutani, Chikahide
, Hanaoka, Fumio
, McCulloch, Scott D.
, Kokoska, Robert J.
, Iwai, Shigenori
in
Base Pairing
/ Biological and medical sciences
/ Deoxyribonucleic acid
/ DNA
/ DNA - biosynthesis
/ DNA - chemistry
/ DNA - genetics
/ DNA - metabolism
/ DNA Damage
/ DNA polymerase
/ DNA-Directed DNA Polymerase - metabolism
/ Fundamental and applied biological sciences. Psychology
/ Humanities and Social Sciences
/ Humans
/ Hydrogen Bonding
/ letter
/ Molecular and cellular biology
/ Molecular genetics
/ multidisciplinary
/ Mutagenesis
/ Pyrimidine Dimers - genetics
/ Pyrimidine Dimers - metabolism
/ Replication
/ Science
/ Science (multidisciplinary)
/ Skin cancer
/ Sulfolobus - enzymology
/ thymidine dimers
2004
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Preferential cis–syn thymine dimer bypass by DNA polymerase η occurs with biased fidelity
Journal Article
Preferential cis–syn thymine dimer bypass by DNA polymerase η occurs with biased fidelity
2004
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Overview
Human DNA polymerase η (Pol η) modulates susceptibility to skin cancer by promoting DNA synthesis past sunlight-induced cyclobutane pyrimidine dimers that escape nucleotide excision repair (NER)
1
,
2
. Here we have determined the efficiency and fidelity of dimer bypass. We show that Pol η copies thymine dimers and the flanking bases with higher processivity than it copies undamaged DNA, and then switches to less processive synthesis. This ability of Pol η to sense the dimer location as synthesis proceeds may facilitate polymerase switching before and after lesion bypass. Pol η bypasses a dimer with low fidelity and with higher error rates at the 3′ thymine than at the 5′ thymine. A similar bias is seen with
Sulfolobus solfataricus
DNA polymerase 4, which forms a Watson–Crick base pair at the 3′ thymine of a dimer but a Hoogsteen base pair at the 5′ thymine (ref.
3
). Ultraviolet-induced mutagenesis is also higher at the 3′ base of dipyrimidine sequences
4
,
5
,
6
. Thus, in normal people and particularly in individuals with NER-defective xeroderma pigmentosum who accumulate dimers, errors made by Pol η during dimer bypass could contribute to mutagenesis and skin cancer.
Publisher
Nature Publishing Group UK,Nature Publishing,Nature Publishing Group
Subject
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