Translesion synthesis by POLI

Stable Identifier
Homo sapiens
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DNA polymerase iota (POLI) is a Y family DNA polymerase with an active site that favours Hoogsteen base pairing instead of Watson-Crick base pairing. POLI-mediated Hoogsteen base pairing and rotation of template purines from anti to syn conformation serves as a mechanism to displace adducts on template G or template A that interfere with DNA replication, or to allow base pairing of damaged purines with a disrupted Watson-Crick edge but an intact Hoogsteen edge (Nair et al. 2004, Nair et al. 2006).

POLI is recruited to DNA damage sites through its interaction with PCNA and REV1. POLI contains a PIP box and two UBMs (ubiquitin binding motifs) that are responsible for POLI binding to monoubiquitinated PCNA (MonoUb:K164-PCNA) (Bienko et al. 2005, Haracska et al. 2005, Bomar et al. 2010). The interaction between POLI and the C-terminus of REV1 is evolutionarily conserved (Kosarek et al. 2003, Guo et al. 2003, Ohashi et al. 2004).

After it incorporates a dNMP opposite to damaged template base, POLI is unable to efficiently elongate the DNA strand further. The elongation step is performed by the polymerase zeta complex (POLZ), composed of REV3L and MAD2L2 subunits (Johnson et al. 2000). The involvement of REV1 and POLZ in POLI-mediated translesion DNA synthesis (TLS) suggests that POLI forms a quaternary complex with REV1 and POLZ, as shown for POLK and proposed for other Y family DNA polymerases (Xie et al. 2012).

Literature References
PubMed ID Title Journal Year
15189446 Interaction of hREV1 with three human Y-family DNA polymerases

Ohashi, E, Murakumo, Y, Kanjo, N, Akagi, J, Masutani, C, Hanaoka, F, Ohmori, H

Genes Cells 2004
10984059 Eukaryotic polymerases iota and zeta act sequentially to bypass DNA lesions

Johnson, RE, Washington, MT, Haracska, L, Prakash, S, Prakash, L

Nature 2000
14657033 Mouse Rev1 protein interacts with multiple DNA polymerases involved in translesion DNA synthesis

Guo, C, Fischhaber, PL, Luk-Paszyc, MJ, Masuda, Y, Zhou, J, Kamiya, K, Kisker, C, Friedberg, EC

EMBO J. 2003
23143872 Structural insights into the assembly of human translesion polymerase complexes

Xie, W, Yang, X, Xu, M, Jiang, T

Protein Cell 2012
15657443 A single domain in human DNA polymerase iota mediates interaction with PCNA: implications for translesion DNA synthesis

Haracska, L, Acharya, N, Unk, I, Johnson, RE, Hurwitz, J, Prakash, L, Prakash, S

Mol. Cell. Biol. 2005
15254543 Replication by human DNA polymerase-iota occurs by Hoogsteen base-pairing

Nair, DT, Johnson, RE, Prakash, S, Prakash, L, Aggarwal, AK

Nature 2004
16819516 Hoogsteen base pair formation promotes synthesis opposite the 1,N6-ethenodeoxyadenosine lesion by human DNA polymerase iota

Nair, DT, Johnson, RE, Prakash, L, Prakash, S, Aggarwal, AK

Nat. Struct. Mol. Biol. 2006
20159559 Unconventional ubiquitin recognition by the ubiquitin-binding motif within the Y family DNA polymerases iota and Rev1

Bomar, MG, D'Souza, S, Bienko, M, Dikic, I, Walker, GC, Zhou, P

Mol. Cell 2010
18242152 Comparative analysis of in vivo interactions between Rev1 protein and other Y-family DNA polymerases in animals and yeasts

Kosarek, JN, Woodruff, RV, Rivera-Begeman, A, Guo, C, D'Souza, S, Koonin, EV, Walker, GC, Friedberg, EC

DNA Repair (Amst.) 2008
16357261 Ubiquitin-binding domains in Y-family polymerases regulate translesion synthesis

Bienko, M, Green, CM, Crosetto, N, Rudolf, F, Zapart, G, Coull, B, Kannouche, P, Wider, G, Peter, M, Lehmann, AR, Hofmann, K, Dikic, I

Science 2005
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