Napolitano R, Janel-Bintz R, Wagner J, Fuchs R P
UPR 9003, CNRS Cancérogenèse et Mutagenèse Moléculaire et Structurale, ESBS and IRCAD, Strasbourg, France.
EMBO J. 2000 Nov 15;19(22):6259-65. doi: 10.1093/emboj/19.22.6259.
Most organisms contain several members of a recently discovered class of DNA polymerases (umuC/dinB superfamily) potentially involved in replication of damaged DNA. In Escherichia coli, only Pol V (umuDC) was known to be essential for base substitution mutagenesis induced by UV light or abasic sites. Here we show that, depending upon the nature of the DNA damage and its sequence context, the two additional SOS-inducible DNA polymerases, Pol II (polB) and Pol IV (dinB), are also involved in error-free and mutagenic translesion synthesis (TLS). For example, bypass of N:-2-acetylaminofluorene (AAF) guanine adducts located within the NAR:I mutation hot spot requires Pol II for -2 frameshifts but Pol V for error-free TLS. On the other hand, error-free and -1 frameshift TLS at a benzo(a)pyrene adduct requires both Pol IV and Pol V. Therefore, in response to the vast diversity of existing DNA damage, the cell uses a pool of 'translesional' DNA polymerases in order to bypass the various DNA lesions.
大多数生物体都含有最近发现的一类DNA聚合酶(umuC/dinB超家族)的多个成员,这些聚合酶可能参与受损DNA的复制。在大肠杆菌中,只有Pol V(umuDC)被认为对紫外线或无碱基位点诱导的碱基置换诱变至关重要。在此我们表明,根据DNA损伤的性质及其序列背景,另外两种SOS诱导型DNA聚合酶,即Pol II(polB)和Pol IV(dinB),也参与无差错和诱变的跨损伤合成(TLS)。例如,位于NAR:I突变热点内的N:-2-乙酰氨基芴(AAF)鸟嘌呤加合物的绕过,-2移码需要Pol II,但无差错的TLS需要Pol V。另一方面,苯并(a)芘加合物处的无差错和-1移码TLS需要Pol IV和Pol V两者。因此,为应对现有DNA损伤的巨大多样性,细胞使用一组“跨损伤”DNA聚合酶来绕过各种DNA损伤。