ライフサイエンスコーパス: Pol iota

1 tic properties of human DNA polymerase iota (pol iota).

2 ly, 8-oxoguanine significantly blocked human Pol iota.

3 s earlier in mice concomitantly deficient in pol iota.

4 d for bypass ability and fidelity with human pol iota.

5 is consistent with Hoogsteen base pairing by pol iota.

6 e incorporation opposite template purines by Pol iota.

7 However, human DNA polymerase iota (Pol iota), a member of the Y family of DNA polymerases,

8 is rotated into the syn conformation in the pol iota active site and that dTTP misincorporation by p

9 late purines adopt a syn conformation in the Pol iota active site, enabling the formation of a Hoogst

10 and incoming dCTP have revealed that in the Pol iota active site, the templating purine adopts a syn

11 We next examined if Pol iota affected tandem mutations generated by another

12 e kinetic assay, herein we showed that human Pol iota and a two-subunit yeast Pol zeta complex (REV3/

13 on structures of the C-terminal UBM of human pol iota and its complex with ubiquitin.

14 Mouse Pol kappa, Rev7, Pol iota and Pol eta each bind to the same approximately

15 ta) and with two other Y-family polymerases, Pol iota and Pol eta.

16 replicated through N(2),3-epsilonG, whereas pol iota and REV1 yielded only 1-base incorporation.

17 ro results also suggested the involvement of pol iota and/or REV1 in inserting correct dCMP opposite

18 of pol kappa > REV1 > pol eta approximately pol iota, and dTTP misincorporation is the major miscodi

19 o4, RB69, KlenTaq, yeast pol iota, human (h) pol iota, and human pol beta.

20 mice with negligible expression of truncated Pol iota, and knock-in mice that express full-length Pol

21 eract with the Y-family polymerases Pol eta, Pol iota, and Pol kappa, and the Rev1 C terminus mediate

22 Additionally, Pol eta, Pol iota, and Pol zeta, but not Pol kappa, had important

23 eins in vitro demonstrate that both forms of Pol iota are active but that they may differ in substrat

24 and IgM crosslinking-dependent induction of pol iota at 12 h may indicate an SHM "triggering" event

25 hat the constricted active site of wild-type pol iota becomes more spacious in the Y39A variant.

26 t Mn(2+) increases the catalytic activity of pol iota by approximately 30-60,000-fold through a drama

27 re, mapping of the domain structure of human pol iota by controlled proteolysis revealed that the enz

28 imidinic (AP) endonuclease and DNA ligase I, pol iota can use its dRP lyase and polymerase activities

29 d S-cdG in human cells, where Pol eta and/or Pol iota carries out nucleotide insertion opposite the l

30 To test the hypothesis that Pol iota causes the high frequency and abnormal spectrum

31 0 mutations from both strains indicated that Pol iota-compromised mice lost the tandem signature, whe

32 Human pol iota contains two functional UBMs, both contributing

33 Although pol iota deficiency alone had no effect, UV-induced skin

34 pe cells that was diminished in pol eta- and pol iota-deficient mouse cells and abolished in cells de

35 be "at risk" for elevated mutagenesis during pol iota-dependent TLS.

36 the variable region, indicating that loss of Pol iota did not change overall mutagenesis.

37 Human DNA polymerase iota (Pol iota) differs from other DNA polymerases in that it

38 A covalently cross-linked pol iota-DNA complex, representing a trapped intermediat

39 Pol iota effectively bypassed N2-methyl (Me)G and N2-eth

40 Opposite a template abasic site human Pol iota efficiently incorporated a G, less frequently a

41 Human Pol iota encoded by the RAD30B gene is a recently identi

42 pol iota exhibited the greatest activity in the presence

43 This implies that the change in pol iota expression is an early event after UV-mediated

44 We report here that pol iota expression is elevated in breast cancer cells a

45 f breast cancer cells additionally increases pol iota expression with a peak occurring between 30 min

46 families: Pol delta (family B), Pol eta and Pol iota (family Y), and Pol lambda and Pol beta (family

47 experiments revealed a strong preference of pol iota for Mn(2+) even when Mg(2+) is present in a >10

48 Pol iota formed T x G mispairs at a frequency of 10(-2),

49 Thus, our data support the Pol iota gene as a modifier of lung tumorigenesis by alt

50 nt database updating, we have found that the Pol iota gene, encoding the DNA polymerase iota, contain

51 Pol iota had the highest dTTP misincorporation frequency

52 We report here that human pol iota has an intrinsic 5'-deoxyribose phosphate (dRP)

53 We found earlier that human pol iota has deoxyribose phosphate (dRP) lyase activity

54 discovered human enzyme DNA polymerase iota (pol iota) has been shown to have an exceptionally high e

55 lymerases kappa (hDinB1), pol eta (hRad30A), pol iota (hRad30B), and yeast pol zeta (Rev3 and Rev7) i

56 ases (pols), e.g. Dpo4, RB69, KlenTaq, yeast pol iota, human (h) pol iota, and human pol beta.

57 a and three distinct catalytic properties of pol iota implicate it in specialized forms of base excis

58 ollectively, these data reveal functions for pol iota in bypassing UV photoproducts and in delaying t

59 ble body of in vitro evidence for a role for pol iota in DNA lesion bypass, there is no in vivo evide

60 These results suggest a role for human Pol iota in DNA lesion bypass.

61 interaction also impair the accumulation of pol iota in replication foci and Rev1-mediated DNA damag

62 lain the slightly favored dCTP insertion for pol iota in steady-state kinetic analysis.

63 uing possibility that the cation utilized by pol iota in vivo may actually be Mn(2+) rather than Mg(2

64 ivity of dTTP opposite O(6)-methylG by human pol iota, in contrast to the mispairing modes observed p

65 pol iota incorporates and extends NTPs opposite damaged

66 s, the two DNA polymerases act sequentially: Pol iota incorporates deoxynucleotides opposite DNA lesi

67 Because wild-type pol iota incorporates NTPs in a template-specific manner

68 re strongly diminished in cells deficient in pol iota, indicating that pol iota participates in the b

69 rporation studies, pol eta inserted C and A, pol iota inserted T, and pol kappa inserted G.

70 ur results indicate that a single residue in pol iota is able to discriminate between NTPs and dNTPs

71 G compared with N2-EtG by pol eta but not by pol iota is consistent with Hoogsteen base pairing by po

72 he hypothesis that in cells lacking Pol eta, Pol iota is responsible for the high frequency and abnor

73 Thus, polymerization by pol iota is severely inhibited by a bulky group at G N2

74 g to the A, B, or Y family, DNA synthesis by Pol iota is severely inhibited by these N7-modified base

75 ctive site and that dTTP misincorporation by pol iota is the result of Hoogsteen base pairing with th

76 DNA polymerase iota (pol iota) is a conserved Y family enzyme that is implica

77 Human DNA polymerase iota (pol iota) is a member of the Y-family of low fidelity le

78 DNA polymerase iota (Pol iota) is an attractive candidate for somatic hypermu

79 DNA polymerase iota (pol iota) is one of several recently discovered DNA poly

80 in Pol eta or Pol zeta, but not Pol kappa or Pol iota, led to pronounced drops in bypass efficiencies

81 Overall, our data strongly suggest that pol iota may be involved in the generation of both incre

82 advantageous mode of Hoogsteen base pairing; pol iota may play a limited role in translesion synthesi

83 That pol iota may play a role in the higher mutation frequenc

84 An approximately 4-fold increase pol iota mRNA occurs within 12 h when cocultured with T

85 The Y39A "steric gate" pol iota mutant is considerably more active in the prese

86 Neither pol iota nor pol zeta, either alone or in combination, w

87 The results support a model where Pol iota occasionally accesses the replication fork to g

88 tter than did pol kappa and much better than pol iota or delta.

89 n the isogenic cells deficient in Pol kappa, Pol iota or Pol zeta, suggesting the mutual involvement

90 mozolomide efficacy, whereas a deficiency in pol-iota or pol-lambda did not increase temozolomide-med

91 ype mice to mice lacking functional pol eta, pol iota, or both.

92 ype mice to mice lacking functional pol eta, pol iota, or both.

93 cells deficient in pol iota, indicating that pol iota participates in the bypass of UV photoproducts

94 To test the hypothesis that pol iota performs TLS in cells, we compared UV-induced m

95 To investigate whether human Pol iota plays a role in lesion bypass we examined the r

96 factor with dRP lyase activity (pol lambda, pol iota, pol theta and Ku70) were found to remove the 5

97 Interestingly, whereas pol iota preferentially misinserts G opposite T by a fac

98 Altered expression of POL iota protein and an amino acid-changing nucleotide p

99 We find that, whereas Pol eta and Pol iota provide alternate pathways for mutagenic TLS, s

100 Purified human Pol iota responded to a template TT (6-4) photoproduct b

101 increasing concentrations of purified human Pol iota, resulting in predominant C and less frequent A

102 In vitro replication studies of Pol iota show that it replicates past 5'T-T3' and 5'T-U3

103 ts for dCTP and dTTP with pol eta and kappa; pol iota showed a strong preference for dTTP.

104 To bypass damage, Pol iota specifically incorporates deoxynucleotides oppo

105 To determine whether pol iota status affects cancer susceptibility, we compar

106 e proximity to the templating residue in the Pol iota ternary complex, have indicated that both facto

107 , and knock-in mice that express full-length Pol iota that is catalytically inactive.

108 Here, we evaluate the ability of pol iota to incorporate NTPs during DNA synthesis.

109 ) also dramatically increased the ability of pol iota to traverse a variety of DNA lesions in vitro.

110 senting BER intermediates, and we found that pol iota was able to complement the in vitro single-nucl

111 Opposite an AAF-adducted guanine, human Pol iota was able to incorporate predominantly a C.

112 uction in mutation frequency was found after pol iota was immunodepleted from nuclear extracts of the

113 In contrast, human Pol iota was largely unresponsive to a template TT cis-s

114 The fidelity of pol iota was measured at RGYW hot- and non-hot-spot sequ

115 To identify a role for Pol iota, we analyzed mutations in two strains of mice w

116 and N7 hydrogen bonding to DNA synthesis by Pol iota, we have examined its proficiency for replicati

117 Of interest is human DNA polymerase iota (pol iota), which has been implicated in TLS of oxidative

118 theta, pol eta, Rev1, pol zeta and, perhaps, pol iota, which are error-prone and crucially insert mis

119 an gene, hRAD30B, encodes the DNA polymerase Pol iota, which misincorporates deoxynucleotides at a hi

120 work from this laboratory using full-length pol iota, which showed that dTTP incorporation occurs wi

121 fespan XPV cell line expressing two forms of Pol iota, whose frequency of UV-induced mutations is twi

122 Crystal structures of pol iota with N(2),3-epsilonG paired to dCTP and dTTP re

123 Crystal structures of the truncated form of pol iota with O(6)-methylG as the template base and inco

124 The crystal structures of Pol iota with template A and incoming dTTP and with temp

125 biological implications, as that would endow Pol iota with the ability to replicate through lesions w

126 Pol iota worked in conjunction with pol kappa, but not w