Translesion synthesis polymerases are dispensable for C. elegans reproduction but suppress genome scarring by polymerase theta-mediated end joining

English version

Autoři: Ivo van Bostelen ^aff001; Robin van Schendel ^aff001; Ron Romeijn ^aff001; Marcel Tijsterman ^aff001
Působiště autorů: Department of Human Genetics, Leiden University Medical Center, Leiden, The Netherlands ^aff001; Institute of Biology Leiden, Leiden University, Leiden, the Netherlands ^aff002
Vyšlo v časopise: Translesion synthesis polymerases are dispensable for C. elegans reproduction but suppress genome scarring by polymerase theta-mediated end joining. PLoS Genet 16(4): e32767. doi:10.1371/journal.pgen.1008759
Kategorie: Research Article
doi: https://doi.org/10.1371/journal.pgen.1008759

Souhrn

Bases within DNA are frequently damaged, producing obstacles to efficient and accurate DNA replication by replicative polymerases. Translesion synthesis (TLS) polymerases, via their ability to catalyze nucleotide additions to growing DNA chains across DNA lesions, promote replication of damaged DNA, thus preventing checkpoint activation, genome instability and cell death. In this study, we used C. elegans to determine the contribution of TLS activity on long-term stability of an animal genome. We monitored and compared the types of mutations that accumulate in REV1, REV3, POLH1 and POLK deficient animals that were grown under unchallenged conditions. We also addressed redundancies in TLS activity by combining all deficiencies. Remarkably, animals that are deficient for all Y-family polymerases as well as animals that have lost all TLS activity are viable and produce progeny, demonstrating that TLS is not essential for animal life. Whole genome sequencing analyses, however, reveal that TLS is needed to prevent genomic scars from accumulating. These scars, which are the product of polymerase theta-mediated end joining (TMEJ), are found overrepresented at guanine bases, consistent with TLS suppressing DNA double-strand breaks (DSBs) from occurring at replication-blocking guanine adducts. We found that in C. elegans, TLS across spontaneous damage is predominantly error free and anti-clastogenic, and thus ensures preservation of genetic information.

Klíčová slova:

Animal genomics – Caenorhabditis elegans – DNA damage – DNA replication – Invertebrate genomics – Mutagenesis – Mutation – Polymerases

Zdroje

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