Abstract:
:We describe here the error specificity of mammalian DNA polymerase eta (pol eta), an enzyme that performs translesion DNA synthesis and may participate in somatic hypermutation of immunoglobulin genes. Both mouse and human pol eta lack intrinsic proofreading exonuclease activity and both copy undamaged DNA inaccurately. Analysis of more than 1500 single-base substitutions by human pol eta indicates that error rates for all 12 mismatches are high and variable depending on the composition and symmetry of the mismatch and its location. pol eta also generates tandem base substitutions at an unprecedented rate, and kinetic analysis indicates that it extends a tandem double mismatch about as efficiently as other replicative enzymes extend single-base mismatches. This ability to use an aberrant primer terminus and the high rate of single and double-base substitutions support the idea that pol eta may forego strict shape complementarity in order to facilitate highly efficient lesion bypass. Relaxed discrimination is further indicated by pol eta infidelity for a wide variety of nucleotide deletion and addition errors. The nature and location of these errors suggest that some may be initiated by strand slippage, while others result from additional mechanisms.
journal_name
J Mol Bioljournal_title
Journal of molecular biologyauthors
Matsuda T,Bebenek K,Masutani C,Rogozin IB,Hanaoka F,Kunkel TAdoi
10.1006/jmbi.2001.4937keywords:
subject
Has Abstractpub_date
2001-09-14 00:00:00pages
335-46issue
2eissn
0022-2836issn
1089-8638pii
S0022-2836(01)94937-Xjournal_volume
312pub_type
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