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A postincision-deficient TFIIH causes replication fork breakage and uncovers alternative Rad51- or Pol32-mediated restart mechanisms.
Mol Cell. 2010 Mar 12; 37(5):690-701.MC

Abstract

Homologous recombination is a major double-strand break (DSB) repair mechanism that acts during the S and G2 phases. In contrast, nucleotide excision repair (NER) is a major pathway for the repair of DNA bulky adducts that is unrelated to replication. We show that replication can be strongly disturbed in a specific type of rad3/XPD NER mutant of TFIIH, causing replication fork breakage. In contrast to classical NER-deficient mutations, the S. cerevisiae rad3-102 allele, which has a minimal impact on UV resistance, channels bulky adducts into DSBs. rad3-102 allows Rad1/XPF- and Rad2/XPG-catalyzed DNA incisions but fails to perform postincision steps retaining TFIIH at the damaged site. Broken forks are rescued by MRX-Rad52-Rfc1-dependent recombination via two types of replication restart mechanisms, one being Rad51 dependent and the other Pol32 dependent. Our results define the genetic and molecular hallmarks of replication fork breakage and restart and bring insights to understand specific NER-related human syndromes.

Authors+Show Affiliations

Centro Andaluz de Biología Molecular y Medicina Regenerativa CABIMER, Universidad de Sevilla-CSIC, Av. Américo Vespucio s/n, 41092 Sevilla, Spain.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

20227372

Citation

Moriel-Carretero, María, and Andrés Aguilera. "A Postincision-deficient TFIIH Causes Replication Fork Breakage and Uncovers Alternative Rad51- or Pol32-mediated Restart Mechanisms." Molecular Cell, vol. 37, no. 5, 2010, pp. 690-701.
Moriel-Carretero M, Aguilera A. A postincision-deficient TFIIH causes replication fork breakage and uncovers alternative Rad51- or Pol32-mediated restart mechanisms. Mol Cell. 2010;37(5):690-701.
Moriel-Carretero, M., & Aguilera, A. (2010). A postincision-deficient TFIIH causes replication fork breakage and uncovers alternative Rad51- or Pol32-mediated restart mechanisms. Molecular Cell, 37(5), 690-701. https://doi.org/10.1016/j.molcel.2010.02.008
Moriel-Carretero M, Aguilera A. A Postincision-deficient TFIIH Causes Replication Fork Breakage and Uncovers Alternative Rad51- or Pol32-mediated Restart Mechanisms. Mol Cell. 2010 Mar 12;37(5):690-701. PubMed PMID: 20227372.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A postincision-deficient TFIIH causes replication fork breakage and uncovers alternative Rad51- or Pol32-mediated restart mechanisms. AU - Moriel-Carretero,María, AU - Aguilera,Andrés, PY - 2009/06/02/received PY - 2009/11/02/revised PY - 2009/12/24/accepted PY - 2010/3/16/entrez PY - 2010/3/17/pubmed PY - 2010/4/14/medline SP - 690 EP - 701 JF - Molecular cell JO - Mol Cell VL - 37 IS - 5 N2 - Homologous recombination is a major double-strand break (DSB) repair mechanism that acts during the S and G2 phases. In contrast, nucleotide excision repair (NER) is a major pathway for the repair of DNA bulky adducts that is unrelated to replication. We show that replication can be strongly disturbed in a specific type of rad3/XPD NER mutant of TFIIH, causing replication fork breakage. In contrast to classical NER-deficient mutations, the S. cerevisiae rad3-102 allele, which has a minimal impact on UV resistance, channels bulky adducts into DSBs. rad3-102 allows Rad1/XPF- and Rad2/XPG-catalyzed DNA incisions but fails to perform postincision steps retaining TFIIH at the damaged site. Broken forks are rescued by MRX-Rad52-Rfc1-dependent recombination via two types of replication restart mechanisms, one being Rad51 dependent and the other Pol32 dependent. Our results define the genetic and molecular hallmarks of replication fork breakage and restart and bring insights to understand specific NER-related human syndromes. SN - 1097-4164 UR - https://www.unboundmedicine.com/medline/citation/20227372/A_postincision_deficient_TFIIH_causes_replication_fork_breakage_and_uncovers_alternative_Rad51__or_Pol32_mediated_restart_mechanisms_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1097-2765(10)00125-5 DB - PRIME DP - Unbound Medicine ER -