# REPAIR AND RECOMBINATION IN RADIATION-SENSITIVE CELLS

> **NIH NIH R01** · UNIVERSITY OF TX MD ANDERSON CAN CTR · 1993 · $106,264

## Abstract

It is generally accepted that recombinational repair is an important
aspect of DNA damage processing in prokaryotes and yeast.  However, few
studies have directly assessed whether shared pathways for DNA repair and
genetic recombination exist in mammalian cells.  Recently, the cloning
of mammalian genes complementing DNA repair-deficient phenotypes and the
discovery of their potential relationships to RAD genes in Saccharomyces
cerevisiae has revealed the prospect of addressing the issue of shared
roles for DNA repair genes in both DNA repair and mitotic recombination
pathways in mammalian cells.  This issue is of particular interest and
importance to carcinogenesis since loss of heterozygosity, a hallmark of
malignant conversion in many cancers, can occur through mitotic
recombination mechanisms.  In this application, they intend to
investigate the role of a mammalian DNA repair/recombination gene, ERCC1,
in mitotic recombination and repair in mammalian cells.  The nature of
a number of different mutations in the ERCC1 gene will be determined by
DNA sequencing after reverse transcription polymerase chain reaction
amplification of RNA from CHO cell ERCC1 mutants.  CHO cell lines in
which the ERCC1 gene disrupted or otherwise altered by targeted
homologous recombination will be generated and characterized with respect
to repair and recombination phenotypes.  These "knock-out" mutants will
be engineered by gene transfer methods to contain heteroallelic gene
duplications designed for the testing of specific hypotheses regarding
whether the ERCC1 gene is involved in mitotic recombination and targeted
recombination in mammalian cells, and how the mechanisms of spontaneous
and induced mitotic recombination in mammalian cells may resemble those
of yeast.  An ERCC1 minigene plasmid will be used to complement knock-out
mutants, and site-directed and random mutagenesis techniques will be used
to specifically alter regions of ERCC1 prior to complementation.
Epistatis between ERCC1 and other repair genes will be investigated.
These experimental approaches will determine what role the ERCC1 repair
gene may play in pathways of mitotic recombination in mammalian cells,
and will increase our understanding of DNA repair and recombination in
mechanisms of genome alteration and carcinogenesis.

## Key facts

- **NIH application ID:** 3173917
- **Project number:** 2R01CA036361-09A2
- **Recipient organization:** UNIVERSITY OF TX MD ANDERSON CAN CTR
- **SAM.gov UEI:** S3GMKS8ELA16
- **Principal Investigator:** Rodney S Nairn
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $106,264
- **Award type:** 2
- **Project period:** 1983-12-01 → 1996-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3173917

## Citation

> US National Institutes of Health, RePORTER application 3173917, REPAIR AND RECOMBINATION IN RADIATION-SENSITIVE CELLS (2R01CA036361-09A2). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3173917. Licensed CC0.

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