Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-762
Crespan, E; Hübscher, U; Maga, G (2007). Error-free bypass of 2-hydroxyadenine by human DNA polymerase lambda with Proliferating Cell Nuclear Antigen and Replication Protein A in different sequence contexts. Nucleic Acids Research, 35(15):5173-5181.
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1,2-dihydro-2-oxoadenine (2-OH-A), a common DNA lesion produced by reactive oxygen species, is a strong replicative block for several DNA polymerases (DNA pols). We have previously shown that various bases can be misincorporated opposite the 2-OH-A lesion and the type of mispairs varies with either the sequence context or the type of DNA pol tested. Here, we have analysed the ability of the human pol family X member DNA pol lambda, to bypass the 2-OH-A lesion. DNA pol lambda can perform error-free bypass of 2-OH-A when this lesion is located in a random sequence, whereas in a repeated sequence context, even though bypass was also largely error-free, misincorporation of dGMP could be observed. The fidelity of translesion synthesis of 2-OH-A in a repeated sequence by DNA pol lambda was enhanced by the auxiliary proteins Proliferating Cell Nuclear Antigen (PCNA) and Replication Protein A (RP-A). We also found that the DNA pol lambda active site residue tyrosine 505 determined the nucleotide selectivity opposite 2-OH-A. Our data show, for the first time, that the 2-OH-A lesion can be efficiently and faithfully bypassed by a human DNA pol lambda in combination with PCNA and RP-A.
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|Item Type:||Journal Article, refereed, original work|
|Communities & Collections:||05 Vetsuisse Faculty > Institute of Veterinary Biochemistry and Molecular Biology|
|Dewey Decimal Classification:||570 Life sciences; biology|
|Deposited On:||11 Feb 2008 12:18|
|Last Modified:||27 Nov 2013 23:57|
|Publisher:||Oxford University Press|
|Additional Information:||Full final text Oxford Journal|
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