Reactome | DNA Damage Bypass

DNA Damage Bypass

Stable Identifier

R-HSA-73893

DOI

10.3180/REACT_2174.4

Type

Pathway

Species

Homo sapiens

Compartment

nucleoplasm

ReviewStatus

5/5

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In addition to various processes for removing lesions from the DNA, cells have developed specific mechanisms for tolerating unrepaired damage during the replication of the genome. These mechanisms are collectively called DNA damage bypass pathways. The Y family of DNA polymerases plays a key role in DNA damage bypass.

Y family DNA polymerases, REV1, POLH (DNA polymerase eta), POLK (DNA polymerase kappa) and POLI (DNA polymerase iota), as well as the DNA polymerase zeta (POLZ) complex composed of REV3L and MAD2L2, are able to carry out translesion DNA synthesis (TLS) or replicative bypass of damaged bases opposite to template lesions that arrest high fidelity, highly processive replicative DNA polymerase complexes delta (POLD) and epsilon (POLE). REV1, POLH, POLK, POLI and POLZ lack 3'->5' exonuclease activity and exhibit low fidelity and weak processivity. The best established TLS mechanisms are annotated here. TLS details that require substantial experimental clarification have been omitted. For recent and past reviews of this topic, please refer to Lehmann 2000, Friedberg et al. 2001, Zhu and Zhang 2003, Takata and Wood 2009, Ulrich 2011, Saugar et al. 2014.

Literature References

PubMed ID	Title	Journal	Year
25038291	Tolerating DNA damage during eukaryotic chromosome replication Saugar, I, Tercero, JA, Ortiz-Bazán, MA	Exp. Cell Res.	2014
21605556	Timing and spacing of ubiquitin-dependent DNA damage bypass Ulrich, HD	FEBS Lett.	2011
10925197	Replication of UV-damaged DNA: new insights into links between DNA polymerases, mutagenesis and human disease. Lehmann, AR	Gene	2000
11595180	Error-prone DNA polymerases: novel structures and the benefits of infidelity. Kisker, C, Friedberg, EC, Fischhaber, PL	Cell	2001
19225445	Bypass specialists operate together Wood, RD, Takata, K	EMBO J.	2009
12800216	DNA polymerase zeta: new insight into eukaryotic mutagenesis and mammalian embryonic development. Zhu, F, Zhang, M	World J Gastroenterol	2003